Early inflammatory response of young rabbits attending natural resistance to calicivirus (RHDV) infection.

Young rabbits (i.e. up to 4 weeks of age) are naturally resistant to infection by rabbit haemorrhagic disease virus (RHDV), the same calicivirus that kills more than 90% of adult rabbits in 3 days or less. To characterize this fascinating model of age-related natural resistance to viral infection, we have studied the kinetics (from 6h up to 7 days) of cytokines and of leukocyte subpopulations in the liver (the target organ for calicivirus replication) and spleen (host systemic response) of RHDV infected young rabbits. Infection was associated with early (6h) elevation of proinflammatory cytokines (TNF-α, IL-1, IFN-α, IFN-γ, IL-6, IL-8). We found that all three major leukocyte subpopulations (macrophages, B and T lymphocytes) were increased in the liver 48h after the RHDV inoculation. At 7 days of infection, B and T lymphocytes were still elevated in the liver of the rabbits. In the spleen, both macrophages and B lymphocytes (but not T cells) were also enhanced. At 7 days, anti-RHDV specific antibodies were present in sera of all young rabbits infected by the virus. We conclude that natural resistance of young rabbits to RHDV infection is associated with a rapid and effective inflammatory response by the liver, with few hepatocytes being infected, and also with a sustained elevation in local and systemic B and T cells.

Moderate leukocyte infiltration in the lower turbinate mucosa after a two-week intranasal administration of mometasone furoate, azelastine or salmon calcitonin.

OBJECTIVE: We used light microscopy to search for local changes of the nasal mucosa associated with daily intranasal administration of mometasone furoate (MF), azelastine (AZ) or salmon calcitonin (SC). STUDY DESIGN: Biopsies of the lower nasal turbinate were obtained from four groups of 8 individuals after 14 days of daily administration of a saline solution (control group) or of MF AZ and SC. METHODS: Small biopsies of the anterior portion of the lower nasal turbinate were collected with the help of a Hartmann forceps under direct visual inspection. The samples were processed for light microscopy and morphometric analysis. Inflammatory infiltration (neutrophils and lymphocytes) of the nasal mucosa was evaluated by a semiquantitative method. Unpaired t test and Bernoulli distribution were applied to evaluate statistical differences between data from the different groups of samples. RESULTS: Samples of the turbinate mucosa of all of the drug-treated groups showed a moderate enhancement in infiltrating neutrophils when compared with the samples from the control group. Infiltration of lymphocytes in the turbinate chorion was significantly different from controls only in the MF and AZ-treated groups. CONCLUSIONS: Intranasal treatment with MF AZ or SC does not cause significant changes in the general architecture of the nasal mucosa. A moderate inflammatory response of the turbinate mucosa, that was expressed by leukocyte infiltration of epithelium and chorion, was observed in all of the 3 drug-treated groups of patients after the 2-week course of intranasal deposition of MF, AZ or SC.

Adult rabbits acquire resistance to lethal calicivirus infection by adoptive transfer of sera from infected young rabbits.

Calicivirus infection of adult rabbits induces the so-called rabbit haemorrhagic disease (RHD) that kills 90% or more of the infected animals; in contrast, young rabbits (up to 8-week-old animals) are resistant to the same infectious agent. We report that calicivirus inoculation of young rabbits induced moderate titres of antiviral antibodies. When these rabbits reached adulthood, a second calicivirus inoculation resulted in resistance to RHD and boosting of antibody titres in half of the rabbits. Adoptive transfer of sera from calicivirus-infected young rabbits to naïve adult rabbits conferred resistance to RHD. We conclude that calicivirus infection of young rabbits induces specific anti-calicivirus antibodies that will protect them from RHD when they reach adulthood.

Acute depletion and recovery of peritoneal B-1 lymphocytes in BALB/c mice after a single injection of mercury chloride.

The acute toxicity of mercury (Hg) to B cells was studied in the peritoneal cavity of BALB/c mice, a coelomic space where both B-1 and B-2 subsets of B lymphocytes are present. Up to 24 hr after a single in situ Hg injection, the peritoneal cavity became virtually devoid of lymphocytes, particularly of the B-1 subset. Lymphocyte depletion was more severe for B than T cells. This depletion was associated with partial lymphocyte activation (CD69(+)) at 6 hr of treatment and it was due to apoptosis rather than to necrosis. Partial recovery of both B and T cells was observed in the peritoneal cavity 48 hr after the Hg injection. The phenomenon was followed by a second decrease in peritoneal lymphocytes 72 hr after Hg. Neutrophils that entered the peritoneal cavity because of the Hg injection were resistant to apoptosis. No significant changes in lymphocyte number or subpopulation were found in the spleen and thymus of the mice up to 72 hr after the Hg treatment. We concluded that B lymphocytes were severely affected by the toxic effects of Hg. Our data suggest that Hg-induced unbalance in the repertoire of B cells, of the B-1 subset in particular, may result later in the secretion of the high titres of pathogenic autoantibodies that are found in the Hg-induced lupus disorder of BALB/c mice.

Liver disease in young rabbits infected by calicivirus through nasal and oral routes.

Calicivirus infection causes rabbit haemorrhagic disease (RHD) that kills more than 90% of adult animals, whereas young rabbits are naturally resistant to this viral disease. It has been proposed that the different response of adult and young rabbits to calicivirus infection is due to absence of viral receptors in respiratory and digestive systems of young animals. We have searched for liver disease in 4-week-old rabbits inoculated with a calicivirus suspension by intranasal and oral routes. These young rabbits showed cell damage and mononuclear infiltration of the liver. The hepatic lesions were associated with mild to moderate increase in circulating transaminases. We conclude that the previously reported reduction of viral receptors in the epithelium of respiratory and digestive systems of young rabbits does not inhibit calicivirus from inducing liver disease in these hosts.

Liver enzymes and ultrastructure in rabbit haemorrhagic disease (RHD).

Rabbit haemorrhagic disease (RHD) is caused by a calicivirus infection that kills most adult rabbits 24-72 h after viral inoculation. Two liver enzymes (AST, aspartate aminotransferase, and ALT, alanine aminotransferase) were monitored in blood samples of calicivirus-infected rabbits during the short course of RHD. Values of AST were used to differentiate three stages of hepatocellular degeneration in RHD: mild (up to 20-fold increase in AST), moderate (150-200-fold elevation of AST) and severe (more than 1000-fold elevation in AST). Liver samples of rabbits from these three biochemical stages of hepatocellular degeneration of RHD were studied by transmission electron microscopy to define the fine structure of the hepatocytes. In the mild hepatocellular degeneration there was proliferation (microvesiculation) of the smooth endoplasmic reticulum and swelling of mitochondria into spheroid bodies with loss of cristae. In moderate hepatocellular degeneration, vacuolization of cytoplasm and mitochondrial damage continued to be present, and there was also formation of autophagic vesicles. In the severe hepatocellular degeneration of RHD, the altered mitochondria also showed loss of density of their matrix; rupture of cytoplasmic vacuoles led to the formation of large vesicles. Marked depletion of liver glycogen was also found in this late stage of RHD. These data offer a correlation between biochemical and cytological features of the liver during the hepatocellular degeneration of RHD.

Severe leukopenia and liver biochemistry changes in adult rabbits after calicivirus infection.

Calicivirus infection is the major cause of the severe decrease in the stocks of wild and farm rabbits that has occurred worldwide during the last two decades. Adult rabbits (10-weeks-old) were experimentally infected with a calicivirus inoculum that killed all animals by causing rabbit haemorrhagic disease (RHD) within 24-62 h of infection. The rabbits were used to evaluate blood cell numbers and serum biochemistry every 6h, starting 12h after the inoculation of the caliciviruses. No significant changes in blood parameters were observed in most of the rabbits up to 18 h of infection. Severe leukopenia was seen 6h before death of the infected rabbits; both heterophils and lymphocytes contributed to the decrease in circulating white blood cells. Platelets were also severely decreased in number. Marked enhancement in liver enzymes was seen 6-12 h before death of the infected rabbits. There was also evidence both for cholestasis, as expressed by the elevated levels of direct (conjugated) bilirubin, and for hypoglycemia, an alteration that it is likely to contribute for the seizures that rabbits show during the late stages of RHD. Liver ultrastructure of rabbits that died from RHD revealed extensive hepatocyte vacuolization, severe changes in mitochondrial structure, and depletion of glycogen granules. We conclude that: (i) severe leukopenia characterizes the final hours of calicivirus-induced RHD; (ii) hypoglycemia and cholestasis precede death of rabbits from RHD; (iii) the kinetics of liver enzymes allows an accurate prediction of the time of death of rabbits from calicivirus-induced RHD.

Leukocyte-hepatocyte interaction in calicivirus infection: differences between rabbits that are resistant or susceptible to rabbit haemorrhagic disease (RHD).

Calicivirus infection is lethal for adult rabbits, whereas young rabbits (less than 8-weeks-old) are resistant to the same infectious agent. The virus replicates in the liver and causes a fulminant hepatitis in adult rabbits leading to rabbit haemorrhagic disease (RHD); this is in contrast with the mild and transient hepatitis observed in infected young rabbits. We have used electron microscopy to compare liver leukocyte infiltrates between young (resistant) and adult (susceptible) rabbits, 36-48 h after inoculation of the animals with caliciviruses. In adult rabbits, liver infiltrates were made up mostly of heterophils, and they were located near hepatocytes showing severe cellular damage. In contrast, liver leukocyte infiltrates of RHD-resistant young rabbits were dominated by lymphocytes that depicted membrane contacts with the cell surface of undamaged hepatocytes. We conclude that: (i) the cellular inflammatory response of the liver to calicivirus infection is different in rabbits that are susceptible (adult) or resistant (young) to RHD; (ii) leukocyte infiltration of the adult liver by heterophils is probably directed at the removal of dead hepatocytes, whereas the liver lymphocytic infiltration of young rabbits suggests the expression of viral antigens on the surface of liver cells of the RHD-resistant animals.

Transient decrease in blood heterophils and sustained liver damage caused by calicivirus infection of young rabbits that are naturally resistant to rabbit haemorrhagic disease.

Young rabbits are naturally resistant to rabbit haemorrhagic disease (RHD) caused by the same calicivirus that kills, within 3 days, nearly all adult animals. We have investigated changes in blood leukocytes, and in the morphology and biochemistry of the liver (the organ where caliciviruses replicate) of young rabbits undergoing benign infection by the RHD virus. Four-week-old rabbits were infected with a calicivirus inoculum having a titre of 2(12) haemagglutination units either sacrificed 18, 24, 48 and 72 h later, or kept for follow-up studies up to 21 days after inoculation. The infection caused an acute and transient decrease in blood heterophils, and sustained enhancement in hepatic transaminases. Inflammatory infiltrates of the liver were seen in all animals after 24 h of infection; they had a predominant midlobular location. Hepatocytes could present different degrees of cell damage, including cell death; these lesions were limited to the liver cells located around the inflammatory infiltrates. Liver transaminases peaked 24-48 h after calicivirus infection; this was the same timing when liver infiltration and hepatocyte damage were more evident. No alterations of other parameters of liver biochemistry were observed. We conclude that calicivirus infection of young rabbits causes a subclinical disorder characterised by an acute and transient decrease in circulating heterophils, and focal liver damage that is expressed by intralobular infiltration by heterophils, initially, and, later on, by mononuclear cells. Our finding of persistence of increased values of liver transaminases suggests chronicity of the infection in young rabbits. We propose that, although resistant to RHD, young rabbits infected by calicivirus may be long-term carriers of the infectious agent and, thus, become a major source of transmission of the virus.

Bulging mesothelial cells of the visceral pleura of the rat mimic the network of subpleural lymphatics.

The mesothelial surface of the visceral pleura of the Wistar rat was viewed at high resolution by scanning electron microscopy (SEM). The pleural surface showed exquisite linear arrangements made up of bulging mesothelial cells. They were organized in irregular circles that often presented anastomotic junctures. This arrangement of pleural mesothelial cells mimics the organization of subpleural lymphatics of the lung. A low density of microvilli was seen inside the irregular circles, contrasting with the microvilli-rich mesothelial cells seen on or outside these arrangements. These SEM features of the mesothelium may be related with the formation of microdomains for fluid absorption across the visceral pleura into subpleural lymphatics.

Zonation of ciliated cells on the epithelium of the rat trachea.

We have used scanning electron microscopy (SEM) to screen the entire epithelial surface of the cervical trachea of the adult rat. This scrutiny revealed that the density of ciliated cells along this epithelium follows a repetitive pattern: circular strips of high density of ciliated cells alternate with areas of low density of the same cells. Cilia-poor strips of the tracheal epithelium were seen on areas of cartilage rings; here, ciliated cells made up 32% of the total surface of the tracheal lining. Cilia-rich areas filled the epithelial surface at the tracheal ligaments (i.e., the regions located in-between the rings); here, ciliated cells occupied 65% of the tracheal lumen. In the cilia-poor zones, the density of ciliated cells decreased from its periphery into its center, where cilia were virtually absent. No differences in this pattern of the tracheal epithelium were seen between young adult and older rats. We conclude that the respiratory epithelium expresses density zonation of ciliated cells on the trachea of adult rats. We propose that the high concentration of ciliated cells on the regions of epithelium located at the tracheal ligaments suggests that these zones are electively committed in the clearance of the respiratory airway.

Morphology of trachea in benign human tracheal stenosis: a clinicopathological study of 20 patients undergoing surgery.

Prolonged tracheal intubation of patients often leads to tracheal stenosis (TS), which may require surgical removal of the narrowed portion of the airway. We studied 20 patients with TS who underwent surgical ablation of the stenotic portion of trachea. The morphology of the tracheal segments was characterized and compared with clinical data and with the prognosis for the disease. We found that TS was usually due to an increase in the width of the mucosa as a result of the fibrosis associated with the chronic inflammation. Plasma cells were the predominant leukocyte type seen in the inflammatory infiltrates of the surgically removed portions of narrowed trachea. In the majority of TS samples, the epithelial surface was intact and presented cilia; in contrast, cilia disappeared when the tracheal lumen was completely obliterated. Mucosal cells and glands were also well preserved in TS samples. The need to remove TS segments was often related to previous tracheal surgery, which was also associated with closing of the tracheal lumen and ossification of cartilage rings. We conclude that (a). chronic inflammation and fibrosis are responsible for the narrowing of trachea in TS patients, (b). metaplastic ossification of cartilage rings only occurs after complete obliteration of the tracheal lumen, and (c). loss of cilia and presence of metaplastic bone tissue are indicators of a poor prognosis for TS.

Tracheal transplantation: cytological changes studied by scanning and transmission electron microscopy in the rabbit.

OBJECTIVES: Our goal was to offer a comprehensive cytological study of the changes in the trachea after experimental transplantation of the organ. STUDY DESIGN: Autografting of four tracheal rings was done in rabbits and tracheal samples were observed by electron microscopy from 1 week to 6 months after the surgery was performed. METHODS: Transmission and scanning electron microscopy were used to investigate the fine structure of tracheal samples of rabbits submitted to autotransplantation, and quantitative methods were used to compare several cytological parameters of the different groups of animals. RESULTS: We found that tracheal autografting was associated with acute injury of ciliated cells expressed by loss of more than 90% of cilia density on the tracheal epithelium 1 week after the transplantation was performed. The loss of cilia was balanced by an increase in mucous cells present on the tracheal lumen. Recovery of ciliated cells was observed 1 month after the tracheal autografting was performed. In contrast, only mild cytological modifications were seen in the cartilage tissue of the autografted trachea during the first weeks of transplantation; the structural alterations of the cartilage progressed up to the third month after transplantation, resulting in a moderate tracheal stenosis. CONCLUSIONS: The data indicate that 1) autotransplantation of four tracheal rings is a viable surgical procedure; 2) tracheal grafting causes severe acute changes of the epithelium that are, however, reversible in nature; whereas 3) the initial mild alterations induced by the autografting in the cartilage may evolve into tracheal stenosis.

In utero and postnatal exposure of Wistar rats to low frequency/high intensity noise depletes the tracheal epithelium of ciliated cells.

Chronic exposure of men or rodents to low frequency/high intensity (LFHI) noise causes a number of systemic changes that make up the so-called vibroacoustic disease (VAD), a disorder that includes alterations of the respiratory system, namely, of its epithelial layer. We have investigated here the susceptibility of the tracheal epithelium of Wistar rats to in utero and postnatal exposure to LFHI noise by comparing its ultrastructure with that of the tracheal epithelium of control rats and of animals exposed to LFHI noise only after reaching adulthood (8 weeks of age). Scanning electron microscopy (SEM) of the inner surface of rat trachea was used to determine the relative areas covered by ciliated and non-ciliated cells. In rats that were exposed in utero and postnatally to LFHI noise, we observed that out of 100 microm(2) of tracheal epithelium only 31 +/- 14 microm(2) were covered by cilia, whereas in control rats; ciliated cells occupied an average of 60 +/- 18 microm(2) out of 100 microm(2) of the epithelium; this difference between the two groups was statistically significant (p <0.05). In rats that were exposed to LFHI noise only after reaching adulthood, cilia covered 55 +/- 22 microm(2) out of 100 microm(2) of the luminal surface of the trachea, a value that, although lower than that of controls, was not found to be statistically different. We conclude that (1) the tracheal ciliated cells are damaged by exposure of rats to LFHI noise if the animals are kept under this environmental aggression during in utero and postnatal periods; (2) tracheal ciliated cells from adult rats are more resistant to the deleterious effects of LFHI noise than pleura or lung alveolar cells that were shown before to undergo marked changes upon chronic exposure of rats to LFHI noise. These findings suggest a note of caution regarding pregnant women and young children: they should be prevented from areas where LFHI noise occurs, namely, in aircraft and textile industries where this type of environmental hazard is often present.

NOD mice are resistant to depletion of thymic cells caused by acute stress or infection.

NOD mice spontaneously develop autoimmune diabetes; disease onset in females of our colony of NOD mice usually takes place around the 4th month of age. Diabetes of NOD mice can be modulated by different stress protocols, even though these animals were shown to be resistant to the effects of glucocorticoids on their lymphocytes. We have recently found that the early host inflammatory response to mycobacteria can be strongly modified by stress, the autoimmunity-prone NOD and NZB/W mice being particularly affected. These mice show reduced numbers of granulocytes in the inflammatory cavity after exposure to stress. Mycobacterium avium is an opportunistic agent that is responsible for disseminated infections seen in AIDS patients. Here, we investigated whether the early immune response to M. avium was altered by stress in NOD mice and we compared the stress response of these mice with a non-autoimmune strain, BALB/c mice. The effects of stress on infected BALB/c mice, which like AIDS patients are susceptible to M. avium infection, offers experimental evidence that M. avium infection, if coupled with stress of the host, may accelerate loss of T helper cells. In contrast, in NOD mice, stress or infection significantly increased the number of cells of the thymuses of the animals. Data obtained with NOD mice support the previously reported resistance of NOD mice lymphocytes to glucocorticoids and suggest that there are two distinct signalling pathways involved in the response of NOD lymphocytes to these stress hormones: one leading to apoptosis and the other mediating glucocorticoid inhibition of activation-induced cell death.

A role for CD45RBlow CD38+ T cells and costimulatory pathways of T-cell activation in protection of non-obese diabetic (NOD) mice from diabetes.

Non-obese diabetic (NOD) mice spontaneously develop autoimmune insulin-dependent diabetes mellitus (IDDM). Infection of the animals with mycobacteria, or immunization with mycobacteria-containing adjuvant, results in permanent protection of NOD mice from diabetes and we have recently reported that the phenomenon is associated with increased numbers of interferon-gamma-producing T cells, possessing increased cytotoxic activity, and also with augmented numbers of activated immunoglobulin M-positive (IgM+) B cells. Here, we have investigated whether protection of NOD mice from IDDM was associated with changes on costimulatory pathways of T and B cells, namely CD28/CTLA-4-B7 and CD40-CD40 ligand (CD40L) and we also further characterized protective T helper (Th) cells with regards to the expression of the differentiation markers CD45RB and CD38. We report that Th cells involved in diabetes vaccination of NOD mice by mycobacterial infection seem to belong to CD45RBlo CD38+ phenotype. The protective effect of Mycobacterium avium infection is also associated with increased CD40L and CTLA-4- expressing Th cells and with the generation of a CD40- IgG+ B cells. Our data are consistent with induction by mycobacterial infection of regulatory CD45RBlo CD38+ Th cells with the ability to trigger deletion or anergy of peripheral self-reactive lymphocytes, with shutting down of IgG+ B-cell response. They also implicate a role for IgG+ B cells in the autoimmune aggression of the endocrine pancreas of NOD mice.

The human pericardium in vibroacoustic disease.

INTRODUCTION: One of the main features of vibroacoustic disease (VAD) is the proliferation of the extra-cellular matrix which induces cardiovascular morphological and dynamic changes, and has been evaluated through echo-Doppler. While all subjects exposed to large pressure amplitude (> or =90 dB SPL) and low frequency (< or =500 Hz) (LPALF) for at least 15 yr have thickening of some cardiac structure, most frequently the pericardium, no significant diastolic changes accompany these observations. Echocardiography has become the diagnostic method of choice for the VAD. However, there have been no studies relating the echo-images of pericardial thickening to gross anatomy. METHODS: We present the histology and ultrastructure of the pericardia of four patients who underwent cardiac surgery. RESULTS: The most important findings concern the real thickening of the pericardium (values: 1.11, 1.35, 2.19, and 2.33 mm vs. norm: < or = 0.5 mm), the dynamic arrangements of mesothelial cells in the serosa layer, and the plasticity of the cells found among the multifascicular waveform collagen fibers. We found that the fibrosa of VAD patients has three layers: sandwiched between two thickened layers of normal fibrosa there is a loose tissue layer with vascular, nervous, and adipose structures. CONCLUSION: These features may partially explain why no important diastolic changes are observed in VAD patients in spite of the pericardium thickening.

Morphological changes in rat lung parenchyma exposed to low frequency noise.

BACKGROUND: Airway flow limitation is has been identified in nonsmoker aeronautical technicians who are exposed to long term (> or =10 yr) large pressure amplitude and low frequency (LPALF) noise (> or =90 dB, < or =500 Hz). Considering this work environment, some kind of pulmonary impairment would be expected, given the probable, but not de facto, existence of fuel exhausts and vapors. In the course of morphofunctional studies of rat pleura exposed to LPALF noise environments, intense subpleural fibrosis was identified. Thus, we decided to study the deep lung parenchyma of these noise-exposed rodents. METHODS: One group of five Wistar rats was exposed to LPALF noise for a cumulative 4000 h, and another of five rats were exposed for a cumulative of 5000 h. The control group consisted of 10, age-matched, Wistar rats that were kept in the same conditions, but in silence. Fragments of lung parenchyma were extracted after sacrifice, and processed for light microscopy, and for scanning and transmission electron microscopy. RESULTS: Focal interstitial fibrosis of the deep lung parenchyma were identified as well as changes in the small bronchial cilia. The amount of brush cells was increased in the locations where microvilli were abnormal. An obvious increase of alveolar type II pneumocyte cells was observed with numerous, large and confluent lamellar bodies. DISCUSSION: In contrast with the normal lung morphology observed in the control group, changes in the extra-cellular matrix and epithelial cells were identified in the exposed rats. No fuel exhaust, vapors or dust were present in the environment of the noise-exposed rats. These results, linked with the respiratory disorders identified in noise-exposed humans, strongly suggest that LPALF noise is an agent of pulmonary fibrosis.

The effect of chronic exposure to low frequency noise on rat tracheal epithelia.

INTRODUCTION: Vibroacoustic Disease (VAD) is a multi-systemic entity caused by occupational or chronic exposure to large pressure amplitude and low frequency (LPALF) noise (> or = 90 dB SPL, < or = 500 Hz). The clinical picture involves extra-auditory pathology, such as neurological disturbances, respiratory disorders and cardiovascular problems. Among the first complaints of VAD patients are coughing, bronchitis, and inflammation or infection of the oral cavity and the upper respiratory pathways. The goal of ths study was to investigate the effects of occupationally simulated LPALF noise exposure on rat tracheal epithelium to determine if they could explain the symptoms found in VAD patients. METHODS: We exposed 20 Wistar rats to occupationally simulated (8 h x d(-1), 5d x wk(-1)) LPALF noise for an accumulated total of 1236 h. The control group consisted of 10 age-matched rats, kept in equal conditions but in silence. Histological and ultrastructural studies were performed on the tracheal epithelia of both populations. RESULTS: The most dramatic changes were identified in the ciliated cells of the exposed rats. There were frequent images of shaggy or necrotic cilia as well as regularly to partially sheared cilia. Also, there were frequent images of different stages of cilia recovery. CONCLUSION: Occupationally simulated exposure to LPALF noise can cause important changes in ciliated cells rat tracheal epithelia. This may partially explain the clinical findings observed in VAD patients.

Effect low frequency noise exposure on BALB/c mice splenic lymphocytes.

INTRODUCTION: Vibroacoustic disease (VAD) occurs in workers exposed for more 10 yr to large pressure amplitude and low frequency (LPALF) noise (> or = 90dB, < or = 500 Hz). In its initial stages (2 yr exposure), VAD is associated with an increase in infections of the respiratory tract. The purpose of this study is to investigate whether exposure of mice to LPALF noise leads to immunological changes as expressed by the number of different lymphocyte subpopulations in the animals' spleen. METHODS: Flow cytometry analysis of spleen lymphocytes was performed in BALB/c mice that had been exposed to occupationally simulated LPALF noise (8 h x d(-1), 5 d x wk(-1)) for a total of 1272 h (approximately 8 mo). The following surface phenotypes of splenic lymphocytes were quantified: IgM, CD4, CD8. Quantification of splenic lymphocytes from non-exposed, age-matched, control BALB/c mice was also performed. RESULTS: Noise-exposed BALB/c mice had decreased T cells, involving both helper (CD4+) and cytotoxic (CD8+) lymphocytes, and also of IgM+ B lymphocytes. CONCLUSION: The data indicate that relatively short term exposure (3 mo) to LPALF noise induces a decrease in spleen lymphocytes in mice which is particularly significant (p < 0.003) in CD8+ T lymphocytes. The data suggest that exposure to LPALF noise causes changes in the immune system of mice. This is in agreement with previous human studies where VAD patients presented an enhancement in the number of circulating CD8+ lymphocytes.