IL-10 inhibits the synthesis of migration inhibitory factor and migration inhibitory factor-mediated macrophage activation.

IL-10, in addition to being a cytokine synthesis-inhibitory factor, is a cytokine that exerts multiple effects on various cell types. Recombinant human migration inhibitory factor (MIF) inhibits the migration of human monocytes as well as that of guinea pig and murine macrophages. In addition, it has recently been shown to activate human monocyte-derived macrophages to suppress the growth of and/or kill both intracellular parasites and extracellular tumor targets in vitro and to have adjuvant activity in vivo. In this study, we examined the interactions between IL-10 and rMIF. We demonstrate that IL-10 reduces the production of MIF from T cells and abolishes rMIF-mediated migration inhibition of human monocytes. Incubation of IL-10 together with rMIF diminishes rMIF-induced intracellular killing of Leishmania donovani by human monocyte-derived macrophages and inhibits nitric oxide production and nitric oxide synthase activity by murine macrophages.

Comparación de la producción del factor inhibidor de la migración de los leucocitos en recién nacidos y adultos / Comparison of production of leucocyte migration inhibition factor in newborns and adults

Para evaluar la madurez del sistema inmune en recién nacidos que por motivos diagnósticos lo requieren, es imprescindibles conocer los parámetros normales. Conociendo la importancia del factor inhibidor de de la migración de los leucocitos(FIML) y al no tener referencias en cuanto a la producción de esta linfoquina en la etapa neonatal, se decidió comparar la capacidad que tienen los linfocitos T de producir FIML, cuando han sido estimulados con antígenos y con el mitógeno fitohemaglutinina en individuos adultos sanos y niños recién nacidos por parto normal, y en estos últimos se explora la inhibión de la migración de los leucocitos de sangre de cordón umbilical incubados con FIMI, específico para un antígeno. Se concluyó que los recién nacidos no responden a los antígenos de memoria y sí lo hacen a la fitohemaglutinina y al FIML, específico para un antígeno

Comparación de la producción del factor inhibidor de la migración de los leucocitos en recién nacidos y adultos / Comparison of production of leucocyte migration inhibition factor in newborns and adults

Para evaluar la madurez del sistema inmune en recién nacidos que por motivos diagnósticos lo requieren, es imprescindibles conocer los parámetros normales. Conociendo la importancia del factor inhibidor de de la migración de los leucocitos(FIML) y al no tener referencias en cuanto a la producción de esta linfoquina en la etapa neonatal, se decidió comparar la capacidad que tienen los linfocitos T de producir FIML, cuando han sido estimulados con antígenos y con el mitógeno fitohemaglutinina en individuos adultos sanos y niños recién nacidos por parto normal, y en estos últimos se explora la inhibión de la migración de los leucocitos de sangre de cordón umbilical incubados con FIMI, específico para un antígeno. Se concluyó que los recién nacidos no responden a los antígenos de memoria y sí lo hacen a la fitohemaglutinina y al FIML, específico para un antígeno

Synthetic peptides comprising defined sequences of CH-2 and CH-3 domains of human IgG1 induce prostaglandin E2 production from human peripheral blood mononuclear cells.

Synthetic peptides Y48 and Y75 comprising sequences at exposed sites within the CH-2 and CH-3 domains of human IgG1 at a concentration of 10(-5) M, increase PGE2 production by human peripheral blood mononuclear cell (PBMC) cultures. An increase of leukocyte migration inhibitory factor (LMIF) production in PBMC cultures--as a result of synthetic peptide treatment--was also observed. This LMIF activity, to some extent, is attributed to the PGE2 production by the cells; the inhibition of leukocyte migration being abolished by the presence of indomethacine or antibody to PGE2.

Identification of reactive synthetic gliadin peptides specific for coeliac disease.

Gluten intolerance (coeliac disease) is characterised by the development of a small intestinal lesion following exposure to the gliadin fraction after consumption of wheat and related cereals. Cellular immune mechanisms are thought to be responsible for gliadin toxicity, but the toxic sequence/s within gliadin have not been clearly established. A panel of synthetic gliadin peptides was tested using peripheral blood mononuclear cells from coeliac patients and two assays for cell-mediated immunity. Using the indirect leucocyte migration inhibition factor and the macrophage procoagulant activity assays, gliadin peptides which were located in the aminoterminal or the proline-rich domain of the alpha/beta gliadin molecule were coeliac-active. Peptides predicted by T cell algorithms or on the basis of homology to adenovirus Ad12 Elb protein and which were located in the proline-poor gliadin domains were inactive. Protein sequence studies which indicate significant homology in the proline-poor gliadin domains with a number of non-coeliac-toxic seed proteins also supported the hypothesis that the proline-rich domains may be more important in the pathogenesis of coeliac disease.

Indomethacin increases the sensitivity of the monocyte migration inhibition assay.

In ophthalmo-immunological investigations only small samples of ocular tissues and fluid are available and assays which are feasible with very small volumes or cell numbers are mandatory. Indomethacin, which is known to augment the immune response both in vivo and in vitro was therefore tested for its effect on the monocyte migration inhibition (MIF) assay using low cell or antigen doses. The sensitivity of the MIF assay may be greatly increased by adding indomethaci during the first step of the assay. Titration of either the antigen dose, the mononuclear cells number or both per assay, resulted in a 10-50-fold increase in sensitivity of the assay, with a broad inter-individual variability. Increasing the sensitivity of the MIF assay with indomethacin has clear advantages with regard to the number of cells required but also confronts us with a new problem: activation of specific cells that circulate at very low frequencies in non-immunized individuals. The enhanced response could be reversed to some extent by adding prostaglandin E2 together with indomethacin to the first step of the assay. Moreover, adding leukotriene B4 to the first step of the assay had an enhancing effect over a limited concentration range. We conclude that in the presence of indomethacin, the MIF assay provides a highly sensitive technique for the demonstration of cellular immune responses in small samples of biological fluids containing very small numbers of antigen-specific lymphocytes.

Migration inhibition factor in acute serum sickness nephritis.

Monocytes have been demonstrated to play an important role in acute serum sickness (AcSS) nephritis. Because accumulation of monocytes within the glomeruli could be the result of local lymphokine production, we studied migration inhibition factor (MIF) activity in supernatants from glomerular cultures, analyzed its temporal relationship with monocyte and lymphocyte accumulation, and tested the effect of anti-T lymphocyte monoclonal antibody on local MIF production. AcSS was induced in 12 rabbits, and one additional rabbit had antigen elimination without proteinuria. Single nephrectomy was performed at the time of antigen elimination in all animals; the remaining kidney was removed four days (4 rabbits) or 14 days afterwards (5 rabbits). In glomerular cross sections (gcs), lymphocytes were identified using monoclonal antibody M108, and monocytes by nonspecific esterase stain (ES). MIF activity was determined in supernatants of cultures of isolated glomeruli by the agarose microdroplet method. Peak of MIF activity (84.3 +/- 2.6%, SEM) was observed the first day of proteinuria in association with peak of lymphocyte infiltration (1.15 +/- 0.1 lymphocytes/gcs) and monocyte infiltration (2.4 +/- 0.3 mean ES score/gcs). MIF activity diminished by day 4 (66.0 +/- 6.3%) and reached control levels by day 14 (12.8 +/- 3.2%). There was a significant correlation between lymphocyte infiltration and MIF activity (r = 0.776, P less than 0.0001) as well as between MIF activity and monocyte accumulation (r = 0.858, P less than 0.0001). In five additional rabbits with AcSS, glomeruli were isolated, treated successively with M108 and normal rabbit serum, and supernatants harvested from 24-hour cultures were tested for MIF activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphocyte inhibitory and chemotactic factors produced by bursal and thymic lymphocytes.

Bursal (B) and thymic (T) lymphocytes from chickens sensitized to Mycobacterium tuberculosis (PPD) or human gamma globulin (hGG) produced an avian lymphocyte-inhibitory factor designated as LyIF-PPD or LyIF-hGG, respectively. A chemotactic factor (LCF) for peripheral blood leukocytes was elaborated only by T-cells sensitized to PPD and hGG. These factors were partially purified by HPLC and were characterized physiochemically. Maximum inhibitory activity for LyIF-PPD and LyIF-hGG occurred in peak fractions corresponding to molecular weight ranges of 29,000 to 52,000 daltons and 15,000 to 29,000 daltons, respectively. The inhibitory activity of B- and T-LyIF-hGG was lost after chymotrypsin and neuraminidase treatment. Maximum chemotactic activity for LCF-PPD and LCF-hGG was in peak HPLC fractions corresponding to molecular weight ranges of 9,000 to 16,000 daltons and 8,000 to 16,500 daltons, respectively. Chemotactic activity of LCF-PPD and LCF-hGG was lost following chymotrypsin treatment while it was not reduced after neuraminidase treatment. Both inhibitory and chemotactic activities were stable at 56 C for 30 min and resistant to changes in pH from 5 to 9. The precursor molecule for the lymphokine is made after antigen immunization, but activated in the presence of the sensitizing agent.

[The functional characteristics of the interaction of lymphokine-producing lymphocytes with granulocytes of the peripheral blood and skin in dermatosis patients]. / Funktsional'nye osobennosti vzaimodeistviia limfokinprodutsiruiushchikh limfotsitov s granulotsitami perifericheskoi krovi i kozhi bol'nykh dermatozami.

PHA-induced mononuclear production of lymphokines altering leukocyte migration was studied in patients with psoriasis, mycosis, and scabies. The findings evidence that T-cells synthesize leukocyte migration inhibition factor (LMIF) in mycosis and scabies, whereas in psoriasis they produce both LMIF and leukocyte migration stimulation factor (LMSF). Blood leukocytes of mycosis and scabies patients were more sensitive to LMIF than the cells of psoriasis patients. The 'skin fenestra' cells (granulocytes) of these patients were functionally active only in respect of LMIF, even when mononuclears synthesized LMSF, this evidencing the participation of skin leukocytes of psoriasis patients in blockage of the functional activity of LMSF-producing immunocompetent cells.

Senile dementia, Alzheimer type: a distinct entity in the immunosenescence?

Since previous data have provided conflicting results on immunoresponsiveness in senile dementia, Alzheimer type (SDAT), we evaluated the immune function in groups of SDAT patients and aged and young donors. In comparison to the younger subjects, SDAT and aged subjects did not exhibit significant differences in lymphocyte surface markers. Both groups of aged donors showed decreased B cell polyclonal responsiveness in a nonspecific T cell-driven B lymphocyte differentiation system. The use of an antigen-specific induction assay revealed an imbalance of T helper (Th) or T suppressor function in the elderly, while SDAT individuals were characterized by decreased Th activity. At the same time, aged individuals manifested an impairment of leukocyte-inhibiting factor (LIF) and lymphocyte-derived chemotactic factor production; a selective deficit of LIF release was seen in SDAT. Finally, elderly individuals displayed a decline of polymorphonuclear cell (PMN)-mediated functions and monocyte phagocytosis; only a decrease in PMN response was observed in SDAT. These results reveal discrepancies in impaired immune responses between SDAT and aging.

Increased migration inhibition factor production by leukocytes of patients with herpes zoster given the leukocyte ultrafiltrate.

Using the direct leukocyte migration inhibition assay, the cell-mediated immune response was followed in together 47 patients suffering from herpes zoster. Of these, 19 persons were treated with partially purified and concentrated lysed leukocyte ultrafiltrate. Enhancement and/or earlier production of the leukocyte migration inhibition factor--in the presence of varicella-zoster virus antigen--was observed by leukocytes from patients given the ultrafiltrate on days 2-3 since the onset of the vesicular stage of the disease. Highly significant (alpha = 1%, P less than 0.01) differences in the migration inhibition values were observed between non-treated patients and patients given one dose of the ultrafiltrate during the days 3-12 after appearance of the first herpes zoster vesicles; on days 13-30 these values were not significant.

Ethanol and soluble mediators of host response.

Lymphokines serve to modulate host inflammatory response by providing a communication link among cells involved in resistance to infection. In the alcoholic, this system may be impaired due to a combination of the direct effects of ethanol on immunocompetent cells and the soluble factors involved in cell-cell interactions. In this paper, we review the literature on this subject, describe an ethanol-related impairment of migration inhibitory factor activity in the rat, and present a possible mechanism for this alteration.

Regulation of lymphokine response during reinfection by influenza virus. Production of a factor that inhibits lymphokine activity.

Mononuclear cells, obtained from the spleens and lungs of influenza virus-seropositive C57BL/6 mice at 2 to 4 days after re-infection with homologous virus (strain A/Bangkok/1/79), produced a low m.w. factor in vitro that prevents the biologic expression, but not production, of the lymphokine, leukocyte migration inhibition factor (LIF). The low m.w. factor inhibited LIF activity without destroying the LIF molecule inasmuch as simple dialysis restored lymphokine activity to culture supernatants. Production of the low m.w. factor was observed from 2 to 4 days after re-infection, at which time the delayed-type hypersensitivity response to viral Ag was suppressed. In contrast, LIF was produced by splenocytes and lung mononuclear cells obtained at all times tested after re-infection (from 2 to 30 days). Production of the low m.w. factor required re-infection of influenza A virus-seropositive mice with type A virus; re-infection with influenza B virus failed to induce production. Ag specificity was also required in vitro for splenocytes to produce the factor; cells from type A virus-re-infected mice required type A Ag stimulation. Cell depletion studies with mAb plus C revealed that macrophages and T cells along with Ag stimulation were required for factor production by spleen cells. However, mononuclear cells obtained within 4 days from the lungs of re-infected mice did not require in vitro Ag stimulation for production of the low m.w. factor, and factor production was dependent upon the presence of CD4+ (L3T4) cells in the culture. Fractionation of culture supernatants over a Sephadex G-50 column indicated that the factor had a molecular mass of 2 to 3 kDa, and by FPLC chromatofocusing over a Mono P column, the factor eluted at a pH of approximately 8.2. Thus, re-exposure of influenza virus-seropositive mice to homologous virus resulted in the production of a low m.w. factor that prevented the biologic expression of LIF, but not its production. Lymphokines are an important component of the delayed-type hypersensitivity response; the presence of mononuclear cells secreting a low m.w. factor and LIF concomitantly at the site of virus replication (lungs) and the capacity of the factor to block the biologic expression of LIF in vitro suggest that the factor may have a role in the regulation of a delayed-type hypersensitivity response in vivo during re-infection.

Production of leukocyte migration inhibition factor (LIF) and migration stimulation factor (MStF) by CD4+ and CD8+ human lymphocytes subsets and T-cell clones.

The production of the lymphokines leukocyte migration inhibition factor (LIF) and migration stimulation factor (MStF) at the level of CD4+ and CD8+ human lymphocyte subsets was investigated. In a first series of experiments, anti-CD4 and anti-CD8 monoclonal antibodies capable of inhibiting the activation by concanavalin-A (Con-A) of the respective T-cell subset were used. It was observed that when CD8+ cell activation was blocked, LIF was always produced after Con-A activation. When CD4+ cell activation was blocked, MStF was produced in five out of nine experiments (no activity in the other four). The addition of N-acetyl-D-glucosamine to block LIF in supernatants of anti-CD8 treated cells was unable to show evidence of masked MStF activity. In a second series of experiments, T-cell clones were established from continuous growing T-lymphocyte cell lines developed from cultures of Con-A activated normal human leukocyte cultures. The phenotype of 22 clones was determined and their ability to produce LIF or MStF investigated. Four clones produced MStF after Con-A activation and all of them were CD3+, CD4-, CD8+. Three clones produced LIF after Con-A activation and all of them were CD3+, CD4+, CD8-. We conclude that LIF is produced by CD4+ cells and MStF by CD8+ cells.

Activation of B lymphocytes with human serum-treated zymosan.

C3 fragments fixed on zymosan particles were presented to resting human B lymphocytes. The opsonized zymosan (Ops-Z) particles induced release of leukocyte migration inhibitory factor, a slight decrease in mIgD, and a slight increase in the activation marker Blast-2. The B cells did not proceed further along the pathway of activation: they did not respond to B cell growth factor (BCGF) and Ops-Z did not synergize with other activators for BCGF response either. Thus, we found that interaction between C3 fragments and CR2 initiates the activation of human B lymphocytes, but this is limited to the early phase.

In vitro immunosuppressive activities of recently developed anthracycline cytostatics.

The effects of a series of seven anthracycline cytostatics on various human leukocyte functions, namely the production of Migration Inhibition Factor (MIF) by lymphocytes and the production of chemiluminescence by activated polymorphonuclear leukocytes (PMNs), as well as on classical and alternative pathways of activation of human complement were investigated. In addition, lipophilic and electrochemical properties of the compounds were determined, by measuring their High Performance Liquid Chromatography (HPLC) capacity ratio (k') and half-wave reduction potential (E1/2). The antitumor agents under investigation suppressed, in most cases, lymphocyte and PMN functions, whereas complement activity remained unaffected. The extent of suppressive effects showed a good correlation with the lipophilicity of the compounds, while no correlation with reduction potentials was found.

The effect of synthetic peptides corresponding to Fc sequences in human IgG1 on various steps in the B cell activation pathway.

The influence of synthetic peptides comprising sequences in the exposed positions of the Fc region of human IgG 1 was tested on B lymphocyte activation. CH 2 domain peptides having an inhibitory effect on antibody-dependent cellular cytotoxicity, as well as the whole Fc fragment, induced the appearance of the early signs of activation on resting B lymphocytes such as increase in cell volume and HLA-DR antigen expression or leukocyte migration inhibitory factor production. The peptides did not induce proliferation of resting B cells even when B cell growth factor (BCGF)-containing supernatants were added. Exposure to Fc fragment, however, induced a weak proliferation which was significantly enhanced by BCGF. On the other hand, both the Fc fragment and the CH 2 or CH 3 domain peptides enhanced the IgM synthesis of human blood mononuclear cells when a suboptimal dose of pokeweed mitogen was present. This effect was lost when Fc fragment or the peptides were added on the third day of culture. These results suggest that the early steps of B cell activation can be induced by Fc fragment and by small molecular weight Fc peptides, which are potential ligands of Fc receptors. The Fc fragment activates B cells to the state where they respond to BCGF, but the peptides do not possess this activity. Furthermore, both Fc fragment and Fc peptides are able to enhance the IgM synthesis, when accessory cells and the appropriate differentiating factors are present.

[Effect of human regulatory myelopeptides on the elaboration of a factor inhibiting leukocyte migration]. / Vliianie reguliatornykh mielopeptidov cheloveka na vyrabotku faktora, ugnetaiushchego migratsiiu leikotsitov.

Some properties of the regulatory peptides from human bone marrow have been investigated. It has been determined that the activity of the regulatory peptides was different in healthy donors and patients with agammaglobulinemia and paraproteinemia.