Efficacy of meloxicam in a pain model in sheep.

OBJECTIVE: To evaluate the efficacy of the non-steroidal anti-inflammatory drug, meloxicam, in alleviating pain and inflammation and on production-related variables in a model of sterile acute inflammation in sheep. METHODS: Groups of 12 mature Merino ewes received 0, 0.5, 1.0 or 1.5 mg/kg meloxicam subcutaneously 90 min before injection of 0.1 mL turpentine subcutaneously on the anterior aspect of the proximal phalanx of a forelimb. Pain- and inflammation-related variables were assessed at -18, 3, 6, 9, 12, 24, 48 and 72 h relative to meloxicam administration. Daily feed intake and body weight change 7 days later were also assessed. Pain-related variables measured were weight borne on each forelimb, lameness score, time each forelimb was raised in a 20-s interval and tolerance to a noxious mechanical stimulus. Inflammation-related variables measured were skin temperature, limb circumference, body temperature, plasma haptoglobin concentration and peripheral blood leucocyte parameters. RESULTS: Meloxicam was effective in improving all pain-related variables. A dose-dependent response was seen between 0 and 1.0 mg/kg, with no additional benefit provided by 1.5 mg/kg. At a dose rate of 1.0 mg/kg, meloxicam improved weight borne on the turpentine-treated limb by 14%, reduced the time the treated limb was held in a non-weight-bearing posture by 46%, reduced the lameness score by 58% and improved tolerance to pressure by 52%. No significant effects of meloxicam on inflammatory variables or appetite were observed. CONCLUSIONS: Using a validated pain model, the data suggested that 1.0 mg/kg meloxicam provided significant analgesic benefits to sheep.

[The application of the emulsified turpentine baths for the correction of the functional state of the cross-country skiers].

The baths with emulsified turpentine find the wide application in balneotherapy. They produce especially pronounced beneficial prophylactic effects in the patients presenting with microtrombosis and microvascular stasis. Moreover, these baths may be prescribed to improve microcirculation, increase the functional reserves and physical capacity in the athletes. At the same time, the current literature appears to contain no scientific publications on the application of emulsified turpentine baths for the restoration of the physical capacity of the professional ski runners. The lack of relevant information motivated the study reported in the present article. The main objective of the study involving 10 subjects was to evaluate the effectiveness of the modified emulsified turpentine baths as a method by which to restore and enhance the physical capacity of the professional cross-country skiers. The physical capacity of the athletes was evaluated from the results of the bicycle ergometer exercise test with the use of the «Oxycon Pro¼ system. The data obtained suggest that a course of the emulsified turpentine baths increases the activity of the cardiorespiratory system, improves the physical capacity, and enhances the functional reserves of the body in the anaerobic zone.

Ferritin L and Ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions.

Ferritin L (FTL) and Ferritin H (FTH) subunits are responsible for intercellular iron storage. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (APR). Aim of the present study is to demonstrate intracellular localization of ferritin subunits in liver compared with extra hepatic organs of rat under physiological and acute phase conditions. Rats were administered turpentine-oil (TO) intramuscularly to induce a sterile abscess (acute-phase-model) and sacrificed at different time points. Immunohistochemistry was performed utilizing horse-reddish-peroxidise conjugated secondary antibody on 4µm thick section. Liver cytoplasmic and nuclear protein were used for Western blot analysis. By means of immunohistology, FTL was detected in cytoplasm while a strong nuclear positivity for FTH was evident in the liver. Similarly, in heart, spleen and brain FTL was detected mainly in the cytoplasm while FTH demonstrated intense nuclear and a weak cytoplasmic expression. Western blot analysis of cytoplasmic and nuclear fractions from liver, heart, spleen and brain further confirmed mainly cytoplasmic expression of FTL in contrast to the nuclear and cytoplasmic expression of FTH. The data presented demonstrate the differential localization of FTL and FTH within hepatic and extra hepatic organs being FTL predominantly in the cytoplasm while FTH predominantly in nucleus.

Impairment of α(2)-macroglobulin synthesis in experimental hepatopathic rats treated with turpentine oil.

The aim of this study was to investigate the synthesis of α(2)-macroglobulin (α2M) in hepatopathic rats injected with turpentine oil to induce acute inflammation. Hepatopathy was induced by oral administration of acetaminophen at a dose of 1 g/kg daily for 2 weeks or a 25% solution of carbon tetrachloride (CCl(4)) at 2 ml/kg body weight three times per week for 7 weeks. Acute inflammation was induced by intramuscular injection of turpentine oil at a dose of 1.0 ml/kg body weight. Serum concentrations of α2M were measured by enzyme-linked immunosorbent assay. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total protein differed significantly between acetaminophen or CCl(4)-induced hepatopathic rats and acetaminophen control (AA-control) or CCl(4) control (CC-control) rats. Furthermore, pathological examination confirmed hepatopathy in rat livers. Peak serum concentrations and area under the time-concentration curve for α2M showed significant differences between hepatopathic rats and AA-control or CC-control rats. Thus, serum concentrations of α2M did not increase when compared with nontreated rats.

STAT3/NF-κB interactions determine the level of haptoglobin expression in male rats exposed to dietary restriction and/or acute phase stimuli.

Haptoglobin is a constitutively expressed protein which is predominantly synthesized in the liver. During the acute-phase (AP) response haptoglobin is upregulated along with other AP proteins. Its upregulation during the AP response is mediated by cis-trans interactions between the hormone-responsive element (HRE) residing in the haptoglobin gene and inducible transcription factors STAT3 and C/EBP ß. In male rats that have been subjected to chronic 50% dietary restriction (DR), the basal haptoglobin serum level is decreased. The aim of this study was to characterize the trans-acting factor(s) responsible for the reduction of haptoglobin expression in male rats subjected to 50% DR for 6 weeks. Protein-DNA interactions between C/EBP and STAT families of transcription factors and the HRE region of the haptoglobin gene were examined in livers of male rats subjected to DR, as well as during the AP response that was induced by turpentine administration. In DR rats, we observed associations between the HRE and C/EBPα/ß, STAT5b and NF-κB p50, and the absence of interactions between STAT3 and NF-kB p65. Subsequent induction of the AP response in DR rats by turpentine administration elicited a normal, almost 2-fold increase in the serum haptoglobin level that was accompanied by HRE-binding of C/EBPß, STAT3/5b and NF-kB p65/p50, and the establishment of interaction between STAT3 and NF-κB p65. These results suggest that STAT3 and NF-κB p65 crosstalk plays a central role while C/EBPß acquires an accessory role in establishing the level of haptoglobin gene expression in male rats exposed to DR and AP stimuli.

Relationship between production of acute-phase proteins and strength of inflammatory stimulation in rats.

The relationship between intensity of inflammatory stimulation and production of α(2)-macroglobulin (α2M) and α(1)-acid glycoprotein (AAG) in rats was investigated. Sprague-Dawley rats were injected with turpentine oil at doses of 0.05, 0.2 or 0.4 mL/rat. Serum levels of α2M, interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were measured by enzyme-linked immunosorbent assay, and AAG was measured by single radial immunodiffusion. Peak serum levels of α2M and AAG in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. However, no significant differences were observed for peak serum levels of these acute-phase proteins between 0.2 and 0.4 mL/rat. Furthermore, peak serum levels of IL-6 and CINC-1 in rats injected at 0.05 mL/rat were significantly lower than those at 0.2 or 0.4 mL/rat. Thus, the production of these acute-phase proteins has upper limits, even under increased strength of inflammatory stimulation in rats injected with turpentine oil.

Optimal combinations of acute phase proteins for detecting infectious disease in pigs.

The acute phase protein (APP) response is an early systemic sign of disease, detected as substantial changes in APP serum concentrations and most disease states involving inflammatory reactions give rise to APP responses. To obtain a detailed picture of the general utility of porcine APPs to detect any disease with an inflammatory component seven porcine APPs were analysed in serum sampled at regular intervals in six different experimental challenge groups of pigs, including three bacterial (Actinobacillus pleuropneumoniae, Streptococcus suis, Mycoplasma hyosynoviae), one parasitic (Toxoplasma gondii) and one viral (porcine respiratory and reproductive syndrome virus) infection and one aseptic inflammation. Immunochemical analyses of seven APPs, four positive (C-reactive protein (CRP), haptoglobin (Hp), pig major acute phase protein (pigMAP) and serum amyloid A (SAA)) and three negative (albumin, transthyretin, and apolipoprotein A1 (apoA1)) were performed in the more than 400 serum samples constituting the serum panel. This was followed by advanced statistical treatment of the data using a multi-step procedure which included defining cut-off values and calculating detection probabilities for single APPs and for APP combinations. Combinations of APPs allowed the detection of disease more sensitively than any individual APP and the best three-protein combinations were CRP, apoA1, pigMAP and CRP, apoA1, Hp, respectively, closely followed by the two-protein combinations CRP, pigMAP and apoA1, pigMAP, respectively. For the practical use of such combinations, methodology is described for establishing individual APP threshold values, above which, for any APP in the combination, ongoing infection/inflammation is indicated.

Development of a lameness model in sheep for assessing efficacy of analgesics.

OBJECTIVE: To develop a lameness model to assess the efficacy of analgesics for alleviating pain, swelling and systemic signs of inflammation in sheep. PROCEDURES: The response to subcutaneous injection of 0.1 or 0.2 mL turpentine in a forelimb pastern (n = 4 ewes per dose) was examined at 0, 3, 6, 24, 48 and 72 h. In a second experiment, responses were measured at 0, 2, 4, 6, 8, 10, 12 and 24 h in ewes receiving 0.1 mL turpentine ± meloxicam 1 mg/kg IV at 0 h (n = 6 per group). Responses measured included forceplate pressure, skin temperature, limb circumference, nociception, leucocyte count, neutrophil : lymphocyte ratio, haptoglobin and daily feed intake. RESULTS: Turpentine injection caused a decrease in weight borne on the treated limb, increased skin temperature, increased sensitivity at the injection site and leucocytosis by 2 h and increased limb circumference by 4 h. Weight borne and sensitivity of the injected limb returned to control levels after around 24 h, whereas tissue swelling, elevated skin temperature and elevated haptoglobin levels persisted for at least 72 h. Treatment with meloxicam improved weight borne by and tolerance to pressure exerted on the turpentine-injected limb. CONCLUSIONS: The local and systemic signs of inflammation and pain, temporary reduction in function of the affected limb and partial amelioration of some of these changes by the dose of meloxicam used here suggest that injection of turpentine in the lower forelimb provides a suitable model for examining the efficacy of analgesics for alleviation of pain and inflammation in sheep.

Prenatal inflammation-induced hypoferremia alters dopamine function in the adult offspring in rat: relevance for schizophrenia.

Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum non-heme iron, which is common to all types of infections. Adequate iron supply to the fetus is fundamental for the development of the mesencephalic dopamine neurons and disruption of this following maternal infection can affect the offspring's dopamine function. Using a rat model of localized injury induced by turpentine, which triggers the innate immune response and inflammation, we investigated the effects of maternal iron supplementation on the offspring's dopamine function by assessing behavioral responses to acute and repeated administration of the dopamine indirect agonist, amphetamine. In addition we measured protein levels of tyrosine hydroxylase, and tissue levels of dopamine and its metabolites, in ventral tegmental area, susbtantia nigra, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Offspring of turpentine-treated mothers exhibited greater responses to a single amphetamine injection and enhanced behavioral sensitization following repeated exposure to this drug, when compared to control offspring. These behavioral changes were accompanied by increased baseline levels of tyrosine hydroxylase, dopamine and its metabolites, selectively in the nucleus accumbens. Both, the behavioral and neurochemical changes were prevented by maternal iron supplementation. Localized prenatal inflammation induced a deregulation in iron homeostasis, which resulted in fundamental alterations in dopamine function and behavioral alterations in the adult offspring. These changes are characteristic of schizophrenia symptoms in humans.

Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute and chronic arthritic models in albino rats.

The present study was undertaken to assess the activity/anti-inflammatory potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea, turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally, significantly inhibited the castor oil-induced diarrhoea and turpentine oil-induced exudative joint oedema in a dose-dependent manner. Significant inhibitory effect of L. usitatissimum fixed oil was observed in formaldehyde-induced proliferative global oedematous arthritis when given intraperitoneally, with significant checking of the serum glutamic oxaloacetic acid transaminase and serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil showed a significant dose-dependent protective effect against CFA-induced arthritis as well. Secondary lesions produced by CFA due to a delayed hypersensitivity reaction were also reduced in a significant manner. Anti-inflammatory activity of L. usitatissimum fixed oil can be attributed to the presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3) having dual inhibitory effect on arachidonate metabolism resulting in suppressed production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished vascular permeability. These observations suggest possible therapeutic potential of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid arthritis.

Imaging vascular endothelial growth factor (VEGF) receptors in turpentine-induced sterile thigh abscesses with radiolabeled single-chain VEGF.

UNLABELLED: Angiogenesis plays a central role in the pathogenesis of chronic inflammatory disorders. Vascular endothelial growth factor (VEGF) and its receptors are the most important regulators of angiogenesis. We wished to determine whether labeled forms of single-chain VEGF (scVEGF) could be used to image VEGF receptors in a well-characterized model of sterile soft-tissue inflammation induced by intramuscular injection of turpentine. METHODS: Anesthetized adult male Swiss-Webster mice received a 20-microL intramuscular injection of turpentine into the right thigh. At 4, 7, or 10 d later, groups of 3-5 mice were injected via the tail vein with 50 microg of either scVEGF that had been site specifically labeled with Cy5.5 (scVEGF/Cy) or inactivated scVEGF/Cy (inVEGF/Cy) and then examined by fluorescence imaging. At 3, 4, 6, 7, 9, 10, or 12 d, additional groups of 3-5 mice were injected via the tail vein with 74-111 MBq of (99m)Tc-scVEGF (or (99m)Tc-inVEGF) and then examined by SPECT imaging. RESULTS: On days 3 through 10, both forms of scVEGF (scVEGF/Cy and (99m)Tc-scVEGF) showed significantly higher uptake (P < 0.05) in the right (abscessed) thigh than in the contralateral thigh (and higher uptake than the inactivated tracer). Peak uptake occurred on day 7 (3.67 +/- 1.79 [ratio of uptake in abscessed thigh to uptake in normal thigh, mean +/- SD] and 0.72 +/- 0.01 for scVEGF/Cy and inVEGF/Cy, respectively, and 3.49 +/- 1.22 and 1.04 +/- 0.41 for (99m)Tc-scVEGF and (99m)Tc-inVEGF, respectively) and slowly decreased thereafter. Autoradiography revealed peak tracer uptake in the thick irregular angiogenic rim of the abscess cavity on day 9 (5.83 x 10(-7) +/- 9.22 x 10(-8) and 5.85 x 10(-8) +/- 5.95 x 10(-8) percentage injected dose per pixel for (99m)Tc-scVEGF and (99m)Tc-inVEGF, respectively); in comparison, a thin circumscribed rim of uptake was seen with (99m)Tc-inVEGF. Immunostaining revealed that VEGFR-2 (VEGF receptor) colocalized with CD31 (endothelial cell marker) at all time points in the abscess rim, whereas F4/80 (macrophage) immunostaining reached a maximum at day 7 and decreased by day 10. CONCLUSION: The uptake of scVEGF in turpentine-induced abscesses was specific and directly related to VEGFR-2 expression in the neovasculature of the angiogenic rim. Peak tracer uptake coincided with maximum macrophage infiltration, suggesting that scVEGF imaging may be useful for the detection, localization, and monitoring of chronic inflammation in bone, joints, or soft tissues.

Facial pain induces the alteration of transient receptor potential vanilloid receptor 1 expression in rat trigeminal ganglion.

OBJECTIVE: To investigate the involvement of transient receptor potential vanilloid receptor 1 (TRPV1) in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. METHODS: Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil (TO) into rat facial area. Head withdrawal thermal latency (HWTL) and head withdrawal cold latency (HWCL) were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density (OD) value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion (TG), peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis (Vc) on day 3, 5, 7, 14, and 21 after TO injection. RESULTS: HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive (IR) to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae I and the outer zone of laminae II (IIo) of Vc. CONCLUSION: Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminals might play an important role in the development and maintenance of TO-induced inflammatory thermal hyperalgesia and cold pain sensation.

Cyclooxygenase system contributes to the maintenance of post convulsive period of epileptic phenomena in the genetically epileptic El mice.

Recent studies have shown that cytokines and cyclooxygenase (COX)-2 are up-regulated in the brain of human epilepsy patients and animal models of epilepsy. We investigated the effect of inflammatory responses induced by intramuscular injection of turpentine on the epileptic phenomenon in genetically epileptic El mice. As parameters of epileptic seizure, seizure threshold (number of toss-ups to induce convulsion), duration of actual convulsion and duration of post actual convulsive period (period from the offset of convulsion to full recovery) were evaluated. The post actual convulsive period was prolonged without any change of seizure threshold or duration of actual convulsion 24 h after turpentine injection. Although pretreatment with indomethacin for one week did not change the seizure parameters, indomethacin suppressed the prolongation of the post actual convulsive period induced by turpentine. The mRNA expression of IL-1beta, IL-6 and COX-2 in the cerebral cortex was detected by RT-PCR. There was no difference in the mRNA expression in the cerebral cortex before and 24 h after seizure. The mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex were up-regulated 24 h after turpentine injection. On the other hand, the up-regulated mRNA levels of IL-1beta, IL-6 and COX-2 in the cerebral cortex after turpentine treatment were not suppressed by indomethacin. These results suggest that prostaglandins induced with COX-2 in the cerebral cortex seem to play an important role in the maintenance of the post convulsive period, but not in induction and maintenance of the actual convulsive state.

The acute-phase response and serum amyloid A inhibit the inflammatory response to Acinetobacter baumannii Pneumonia.

BACKGROUND: Acinetobacter baumannii is an emerging pathogen in nosocomial pneumonia. Trauma and postsurgical patients display a profound acute-phase protein response and are susceptible to pneumonia. METHODS: To study the way in which the acute-phase response induced by sterile tissue injury influences pulmonary host defense, mice were injected subcutaneously with turpentine or saline in both hind limbs either 2 or 5 days before intranasal inoculation with A. baumannii. RESULTS: Turpentine-injected mice demonstrated strong increases in levels of the acute-phase proteins serum amyloid A (SAA) and serum amyloid P. The inflammatory response to A. baumannii was significantly impaired in turpentine-injected mice, as shown by decreased local cytokine and chemokine levels, reduced neutrophil influx and lung myeloperoxidase activity, less pulmonary inflammation on histological examination, and lower total protein levels in their bronchoalveolar lavage fluid, which was associated with reduced bacterial clearance of A. baumannii. The late acute-phase protein response still caused lower pulmonary cytokine levels and neutrophil recruitment. Furthermore, previous injection of SAA, a major acute-phase protein, also reduced inflammatory responses to A. baumannii pneumonia. CONCLUSIONS: These data suggest that the acute-phase response and SAA inhibit the local inflammatory response to A. baumannii pneumonia, which may facilitate bacterial outgrowth.

Modulation of CYP1A2 and CYP3A6 catalytic activities by serum from rabbits with a turpentine-induced inflammatory reaction and interleukin 6.

Inflammatory reactions reduce the activity of cytochrome P450 isoforms. The aim of the study was to determine the mechanisms underlying the decrease in CYP1A2 and CYP3A6 catalytic activities produced by serum from rabbits with a turpentine-induced inflammatory reaction (S(TIIR)) and interleukin 6 (IL-6). S(TIIR) and IL-6 were incubated with cultured primary hepatocytes from control rabbits (H(CONT)), and from rabbits with a turpentine-induced inflammatory reaction (H(TIIR)) in the absence or presence of pyrrolidine dithiocarbamate (PDTC), an antioxidant and inhibitor of nuclear factor kappaB transcription; 2'-amino-3'-methoxyflavone (PD98059), an inhibitor of extracellular signal-related kinase (Erk1/2); 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580), an inhibitor of p38MAPK; Nomega-nitro-L-arginine methyl ester, an inhibitor of nitric-oxide synthase 2 (NOS2); the combination of PDTC, PD98059, and SB203580; and genistein, an inhibitor of Janus-associated protein tyrosine kinase (JAK). After 4 and 24 h of incubation of H(CONT) with S(TIIR) and IL-6, CYP1A2 activity was reduced without changes in expression; the reduction in activity was partially prevented by the inhibition of JAK, Erk1/2, and NOS2. In H(CONT), S(TIIR) and IL-6 did not affect CYP3A6 activity; however, PDTC reduced CYP3A6 activity by 40 and 80% after 4 and 24 h of incubation. In H(TIIR), S(TIIR) and IL-6 reduced both CYP1A2 and CYP3A6 activities; this decrease is partially prevented by inhibitors of protein tyrosine kinases, Erk1/2, and NOS2. In H(TIIR), SB203580 increased CYP3A6 activity in a dose-dependent manner without changes in protein expression. These results show that the signal transduction pathways mediating the decrease in CYP1A2 and 3A6 activity, produced by S(TIIR) and IL-6, involve JAK, Erk1/2, and NOS2.

Induction of type 3 deiodinase activity in inflammatory cells of mice with chronic local inflammation.

During illness, changes in thyroid hormone metabolism occur, so-called nonthyroidal illness (NTI). NTI has been characterized by a fall of serum T(3) due to decreased extrathyroidal conversion of T(4) into T(3) by liver type 1 deiodinase (D1), without an increase in serum TSH. Type 3 deiodinase (D3) was thought not to play an important role during NTI, but recently it has been shown that D3 activity is up-regulated in liver and skeletal muscle of critically ill patients related to hypoxia. We studied D3 gene expression and activity in liver and muscle/subcutis of mice during illness, which was induced by two different stimuli: bacterial endotoxin (lipopolysaccharide) administration, resulting in an acute systemic response, and a turpentine injection in each hindlimb, resulting in a local sc abscess. Lipopolysaccharide induced a rapid decrease in liver D1 and D3 activity but not skeletal muscle of hindlimb. In contrast, local inflammation induced by turpentine did not decrease liver D1 and D3 activity but increased markedly D3 activity in the muscle/subcutis sample containing the abscess, associated with strongly increased IL-1beta and IL-6 mRNA expression. Inflammatory cells, surrounding the abscess showed D3 and T(3)-transporter monocarboxylate transporter-8 immunoreactivity, whereas muscle cells did not show any immunoreactivity. In conclusion, local inflammation strongly induces D3 activity in inflammatory cells, especially in invading polymorphonuclear granulocytes, suggesting enhanced local degradation of T(3).