Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rats, complete Freund's adjuvant (CFA), injected at the base of the tail, induced a hyperactivation of cellular immune functions and triggered the development of adjuvant arthritis (AA). Before onset of arthritis (Days 9-10 upon CFA), the positive control rats showed significant increases of pituitary prolactin (Prl) mRNA accumulation (Days 3-5). On the other hand, production of pituitary growth hormone (GH) mRNA was significantly reduced from Day 3 onwards. During this early latent period, plasma Prl levels were transiently increased (at least on Day 4), while GH levels were reduced within 8 days (and onwards). Pituitary proopiomelanocortin (POMC) mRNA content progressively decreased with a nadir between Days 6 and 8, accompanied by a loss of the adrenocortical ornithine decarboxylase (ODC) circadian rhythm of activity and a transient reduction of plasma corticosterone (CS) levels (Days 3-6, obvious during the dark phase). At onset of arthritis, the POMC mRNA accumulation and adrenocortical ODC activity increased over their respective baselines. Elevation of plasma CS levels (obvious during the light phase) and important CS-induced thymolysis occurred. Further, hypophysectomized rats did not develop AA. However, hypophysectomized male rats carrying pituitary grafts under the kidney capsule had mild hyperprolactinaemia and developed a worsened arthritic response to CFA, compared to sham-operated controls. On the other hand, intact hyperprolactinaemic male rats showed a delay in the onset and a reduction in the severity of AA. This difference might be due to stimulation of the adrenal cortex in intact pituitary-grafted rats. Such rats showed increased baselines of pituitary POMC mRNA production, adrenocortical ODC activity and plasma CS levels. In addition, during the latent period after CFA, POMC mRNA accumulation, adrenocortical ODC activity and plasma CS levels were only partially suppressed, less than in sham-operated rats. Extensive thymolysis occurred after CFA in these animals--as in the sham-operated rats--but not in the hypophysectomized pituitary-implanted rats. This suggested that in the presence of adrenocortical deficiency, Prl released by the pituitary graft can freely act on the immune system, without being counter-regulated by CS.
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PMID:Hyperprolactinaemia in hypophysectomized or intact male rats and the development of adjuvant arthritis. 147 89

Diverse data link estrogen influences to both the frequency and severity of systemic lupus erythematosus in humans and to murine lupus. A fundamental mechanism of action of estrogen involves the interaction of the hormone with its receptor protein, which is then transformed into the DNA binding form. We measured the concentration of uterine estrogen receptor and its DNA binding in normal BALB/c mice, lupus-prone MRL-lpr/lpr mice, and MRL-lpr/lpr mice that had been treated with 1% difluoromethylornithine (DFMO). Uterine estrogen receptor levels in 20-week-old mice from the 3 groups were not significantly different. In contrast, DNA binding activity was significantly higher in BALB/c mice (mean +/- SD 775 +/- 100 fmoles/mg of DNA) than in untreated MRL-lpr/lpr mice (80 +/- 16 fmoles/mg of DNA) (P less than 0.001). Treatment with 1% DFMO was associated with an increase in uterine estrogen receptor DNA binding (1,100 +/- 218 fmoles/mg of DNA) in MRL-lpr/lpr mice (P less than 0.001). Polyamine levels were 2-6-fold higher in the uterine tissues of untreated MRL-lpr/lpr mice compared with the BALB/c mice and were significantly reduced by DFMO treatment. Our results link uterine polyamine production to a dysfunction of the estrogen receptors in MRL-lpr/lpr mice. Reduction of the polyamine level by the irreversible inhibition of ornithine decarboxylase with DFMO restores estrogen receptor function.
Arthritis Rheum 1991 Jan
PMID:Restoration of the DNA binding activity of estrogen receptor in MRL-lpr/lpr mice by a polyamine biosynthesis inhibitor. 198 79

Cells of the immune system synthesize prolactin and express mRNA and receptors for that hormone. Interleukin 1, interleukin 6, gamma interferon, tumor necrosis factor, platelet activator factor, and substance P participate in the release of prolactin. This hormone is involved in the pathogenesis of adjuvant arthritis and restores immunocompetence in experimental models. In vitro studies suggest that lymphocytes are an important target tissue for circulating prolactin. Prolactin antibodies inhibit lymphocyte proliferation. Prolactin is comitogenic with concanavalin A and induces interleukin 2 receptors on the surface of lymphocytes. Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes. Cyclosporine A interferes with prolactin binding to its receptors on lymphocytes. Hyperprolactinemia has been found in patients with systemic lupus erythematosus. Fibromyalgia, rheumatoid arthritis, and low back pain patients present a hyperprolactinemic response to thyrotropin-releasing hormone. Experimental autoimmune uveitis, as well as patients with uveitis whether or not associated with spondyloarthropathies, and patients with psoriatic arthritis may respond to bromocriptine treatment. Suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine A with significantly less toxicity. Prolactin may also be a new marker of rejection in heart-transplant patients. This body of evidence may have an impact in the study of rheumatic disorders, especially connective tissue diseases. A role for prolactin in autoimmune diseases remains to be demonstrated.
Semin Arthritis Rheum 1991 Apr
PMID:Prolactin, immunoregulation, and autoimmune diseases. 206 74

In male rats, inoculation of Freund's complete adjuvant (FCA, 0.5 mg/rat of Mycobacterium butyricum in paraffin oil) induced high levels of ornithine decarboxylase (ODC) in the hypothalamus and pituitary gland (285% and 245% of controls, respectively, within 12 h to 2 days). ODC activity also was altered in the cerebellum and left neocortex, but not in the right neocortex. This activity reflected a dynamic equilibrium which is influenced by ODC synthesis, degradation, activation, etc. The circadian rhythms of pituitary ODC activity and plasma prolactin level, 3-4 days after FCA, showed that enhancement of enzymatic activity during the dark phase correlated with a marked release of prolactin (Prl). During this early period after FCA, changes in plasma levels of other pituitary hormones were not significant or were less important. Pretreatment with bromocriptine microcapsules inhibited both basal and FCA-induced pituitary ODC activity, as well as Prl secretion. Further, significant increases in plasma luteinizing hormone and adrenocorticotropic hormone were noted from days 4 and 8, respectively, and onwards. Finally, a phase of reduced corticosterone secretion occurred during the latency period. This study shows that FCA influences central nervous system pathways and supports the idea that endogenous Prl is involved in some early events which lead to the development of adjuvant arthritis.
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PMID:Freund's complete adjuvant induces ornithine decarboxylase activity in the central nervous system of male rats and triggers the release of pituitary hormones. 215 4

The objective of the present investigation was to examine the effects of an irreversible inhibitor of ornithine decarboxylase (2R,5R)-6-heptyne-2,5,diamine (methylacetylenic putrescine, MAP) on experimentally induced arthritis in mice. MAP (0.5-0.05%) was administered in drinking water to DBA/1 mice immunized with native chick type II collagen (CII). The development of arthritis was inhibited only in those mice receiving 0.5% MAP; lower doses were ineffective. Putrescine and spermidine levels were decreased and spermine levels were increased in spleen and lymph node cells from drug-treated mice compared to control arthritic mice. Furthermore, when control mice were developing arthritis, serum anti-CII antibody levels were lower in the MAP-treated group. MAP inhibited antibody production early in the immune response to CII; there was an association between inhibition of antibody production and inhibition of the development of arthritis. When MAP was discontinued, the nonarthritic, drug-treated mice did not develop the disease. Late administration of MAP (beginning 19 days after CII immunization) did not affect the incidence or the severity of the arthritis. Cyclophosphamide treatment begun at the same time significantly inhibited the development of the disease. In vitro T cell responses to denatured type II collagen (dCII) in untreated and MAP-treated mice were examined 14 days after immunization with CII. This is a time of peak T cell responsiveness in untreated animals. MAP treatment had no effect on the T cell response to dCII. These results indicate that MAP can prevent the development of CII-induced arthritis, possibly by inhibiting the autoantibody response. Therefore, inhibitors of polyamine biosynthesis deserve further investigation as potential immunosuppressive agents.
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PMID:Methylacetylenic putrescine (MAP), an inhibitor of polyamine biosynthesis, prevents the development of collagen-induced arthritis. 229 95

Arthritis is produced in male rats within 9-10 days after a single injection of Freund's complete adjuvant (FCA) at the base of the tail. When bromocriptine, a dopaminomimetic that suppresses PRL secretion, was given in form of long-acting microcapsules (CBLA) 3 days before FCA, the hind limb swelling was significantly reduced by 70%. Here, we showed that plasma PRL levels were significantly elevated (by 150% over controls) during the 6-day period after FCA, particularly at night. Further, within 1-4 days after FCA inoculation, marked increases in ornithine decarboxylase (ODC) activity occurred in bone marrow, thymus, spleen, and lymph nodes (by 190%, 160%, 80% and 75% over control values, respectively). In FCA-treated rats, the circadian rhythm of thymic ODC showed that an important enhancement of activity occurred during the dark phase, which correlated with the peak of PRL secretion (between 2200-0400 h). Finally, pretreatment with CBLA significantly inhibited the induction of ODC in response to FCA in thymus, spleen, and lymph nodes (by 65%, 80%, and 45%, respectively) and inhibited it more weakly in the bone marrow. This in vivo study leaves little doubt about the existence of a PRL-dependent immuno-stimulatory mechanism, probably involved in the pathogenesis of adjuvant arthritis.
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PMID:Bromocriptine microcapsules inhibit ornithine decarboxylase activity induced by Freund's complete adjuvant in lymphoid tissues of male rats. 258 42

Aging has been associated with attenuation of amplitude and changes in period of many circadian rhythms. The present study was carried out to examine, in young (50 days old) and old (18 months old) rats, whether 24-h rhythms of cell proliferation (as assessed by measuring ornithine decarboxylase activity) and of presynaptic adrenergic and cholinergic markers change in lymph nodes and spleen during Freund's adjuvant-induced arthritis. Groups of young and old Sprague-Dawley rats were studied the day before, and on days 6, 12 and 18 after Freund's adjuvant injection. On day 16 after adjuvant injection, inflammation of hind paws, mainly in the ankle joints, was less marked in old than in young rats. Lymph node and splenic ornithine decarboxylase activity exhibited significant 24-h variations with maximal activity during daily hours. Before treatment, enzyme activity values were significantly lower in old rats in both tissues examined. During the immune reaction, lymph node and splenic ornithine decarboxylase augmented 8-10-fold, with progressively smaller amplitude of daily variations as arthritis developed. In every case, mesor and amplitude of ornithine decarboxylase activity were lowest in old rats. Submaxillary lymph node and splenic tyrosine hydroxylase activity attained maximal values at night. At every time interval after mycobacterium adjuvant injection, amplitude and mesor of tyrosine hydroxylase activity rhythm were lowest in old rats. A maximum in submaxillary lymph node 3H-acetylcholine synthesis occurred at the afternoon. On day 6 and 12 after Freund's adjuvant injection, lymph node 3H-acetylcholine synthesis was significantly smaller in old rats. Day-night differences in submaxillary lymph node or splenic ornithine decarboxylase and tyrosine hydroxylase activities, or in submaxillary lymph node 3H-acetylcholine synthesis, of rats treated with the adjuvant's vehicle, did not differ significantly from those seen in untreated controls. The results are compatible with an age-dependent decline of immune-mediated inflammatory responses. The activity of the central circadian oscillator, driven to the organs in part via the autonomic nervous system, seems also to deteriorate during aging.
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PMID:Diurnal rhythms in ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats during Freund's adjuvant-induced arthritis. 957 84

Young (50 days old) and old (18 months old) Sprague-Dawley rats were injected with mycobacterial Freund's adjuvant to produce an inflammatory disease of the joints and were studied the day before, and on days 6, 12 and 18 after injection. At every postinjection interval examined, old rats had significantly lower circadian amplitudes of pineal melatonin content. On day 18 of arthritis development, decreased levels of pineal melatonin were also seen in young rats. A second study, carried out 18 days after the injection of Freund's complete adjuvant and after 17 daily injections of 10 or 100 microg of melatonin in the evening, indicated that melatonin treatment restored the inflammatory response in old rats (assessed plethysmographically in hind paws) to the level found in young animals. In young rats, an inflammation-promoting effect of 100 microg melatonin could be demonstrated. As a consequence of the immune reaction, submaxillary lymph node and splenic ornithine decarboxylase activity (an index of lymph cell proliferation) augmented significantly, with acrophases of 24-hour rhythms in the afternoon for lymph nodes or in the morning for spleen. Mesor and amplitude of ornithine decarboxylase rhythm were lowest in old rats, while melatonin injection generally augmented its amplitude. Lymph node and splenic tyrosine hydroxylase activity (a presynaptic adrenergic marker) reached maximal values during early night hours while maximal values of [3H]acetylcholine synthesis (a presynaptic cholinergic marker) occurred during the afternoon in lymph nodes. Amplitude and mesor of these rhythms were lowest in old rats, an effect generally counteracted by melatonin treatment. The results suggest that inflammation is accompanied by an age-dependent, significant depression of pineal melatonin synthesis during adjuvant-induced arthritis and a decreased amplitude of the circadian rhythm of immune cell proliferation and autonomic activity in lymph nodes and spleen. These effects are counteracted by injection of melatonin, mainly in old rats.
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PMID:Effect of melatonin on 24-hour rhythms of ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats. 964 17

Wistar male rats were injected s.c. with melatonin (30 microg) or vehicle, 1 h before lights off, for 11 days. Ten days after beginning melatonin treatment, rats received Freund's complete adjuvant or its vehicle s.c., and after 2 days, they were sacrificed at six different time intervals throughout a 24-h cycle. The mitogenic effect of lipopolysaccharide (LPS) and concanavalin A (Con A), the activity of ornithine decarboxylase (ODC) and the relative size of lymphocyte subset populations were measured in submaxillary lymph nodes. In control rats, the mitogenic effects of LPS and Con A and ODC activity peaked during the afternoon. Injection of Freund's adjuvant induced a 10-h shift in the diurnal rhythm of the mitogenic effect of LPS to attain maximal values at night. Melatonin pretreatment blunted the daily variations in the mitogenic activity of Con A or LPS and, when given to Freund's adjuvant-injected rats, augmented mesor and amplitude of diurnal rhythm in ODC activity. Maxima in B cell number occurred at night whereas those of T and B-T cell number occurred during the afternoon. During the early phase of immunization tested, the number of B cells augmented and the amplitude of its diurnal rhythmicity increased both after immunization and following melatonin pretreatment. Maxima of 24-h rhythms in CD4+ and CD4+/CD8+ cell populations occurred during the afternoon while those of CD8+ cells occurred at late night. Melatonin significantly augmented CD4+ cell number and decreased CD8+ cell number; it therefore augmented the CD4+:CD8+ ratio. The results suggest that pretreatment with a pharmacological dose of melatonin exerts immunomodulating effects at an early, preclinical, phase of Freund's adjuvant-induced arthritis in rats.
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PMID:Effect of melatonin treatment on 24-h variations in responses to mitogens and lymphocyte subset populations in rat submaxillary lymph nodes. 1092 88

Old rats had significantly lower values of the amplitude of pineal melatonin content at any time point studied. Complete Freund's adjuvant administration reduced the amplitude of melatonin rhythm. On day 18 of arthritis development, decreased pineal melatonin contents were also seen in young rats. On day 18, a global depressive effect of arthritis development on pineal melatonin content was found. However, prolactin levels increased in old as compared to young rats. Freund's adjuvant administration brought about changes in the secretory pattern of prolactin in young and old animals that are opposite to those described for melatonin. Cell proliferation as assessed by ornithine decarboxylase activity exhibited significant 24-h variations with maximal activity of the enzyme during daily hours, acrophases varying from 13:15 to 16:52 h (lymph nodes). The mesor and amplitude of ornithine decarboxylase activity were lowest in old rats. Melatonin (100 &mgr;g) augmented amplitude of daily rhythm in submaxillary lymph node ornithine decarboxylase activity significantly. These data indicate that melatonin and prolactin change differentially during arthritis development in young and old animals, perhaps indicating opposite effects in the induction and maintenance of adjuvant-arthritis. The changes are compatible with the values of ornithine descarboxylase activity.
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PMID:Effects of melatonin on 24-h rhythms of neuroendocrine and immune changes in Freund's adjuvant-induced arthritis. 1146 9


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