Heat shock protein (hsp), one of the most conserved and ubiquitous proteins from bacteria to mammals, was shown to be strongly immunogenic. These characteristics, i.e. conservation and immunogenicity, and the fact that hsp was the target molecule of some of γ/δT cells placed this molecule at the interface between immunity and tolerance and the role of this molecule on autoimmune and inflammatory disorders has been vigorously investigated. Evidences accumulated so far are highly suggestive of the possible involvement of hsp in clinical disorders but still circumstantial.
Two things must be solved. (1) Why conserved proteins are so immunogenic? Mechanism of molecular mimicry is really at work? (2) Why ubiquitous proteins could be a target of organ-specific autoimmunity?

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Oral gold compound, auranofin (AF), is clinically useful for the treatment of patients with rheumatoid arthritis (RA) as one of the disease modifying anti-rheumatic drugs, although its mechanism of action is not determined yet. In the present study, the effects of auranofin on the production of IgG rheumatoid factor (IgGRF), IgMRF, IL-1β and TNF-α by mononuclear cells (MNC) .
MNC were isolated from 6 RA patients. MNC of each patients were cultured with or without AF for 24 hrs and the supernatants obtained by centrifuga-tion were measured for IL-1β and TNF-α by ELISA kit. The supernatants obtained after 7 day' culture were measured for IgGRF and IgMRF by ELISA.
AF significantly inhibited IgGRF, IgMRF and IL-1β production at its final concentration of 0.375 and 0.75 μg/ml. TNF-α production was also significantly inhibited by physiological concentration of AF. The inhibition by AF of IgGRF, IgMRF, IL-1β and TNF-α production by RA MNC may be one of the mechanisms by which AF shows clinical efficacy.

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Thapsigargin, a hexaoxygenated tetraacylated sesquiterpene lactone isolated from the roots of Thapsia garganica L., is one of non-TPA type tumor promoters that stimulate prostaglandin E₂ production at very low concentrations and induce inflammation when applied topically. Effects of thapsigar-gin on platelet activating factor (PAF) production by rat peritoneal macrophages were examined. Levels of PAF in the conditioned medium and in the cells were determined by radioimmunoassay after extraction of PAF using immunoaffinity mini-columns. It was demonstrated that thapsigargin at concentrations of 3 to 100 ng/ml stimulated production of cell-associated PAF when measured 10 min after incubation. Levels of PAF in the conditioned medium were less than the detectable amount.
The stimulative effect by thapsigargin reached a plateau at a concentration of 30 ng/ml. Time course experiments revealed that the levels of cell-associated PAF showed a peak 10 to 15 min after incubation with thapsigargin at a concentration of 30 ng/ml. The levels were then declined until 40 min after incubation. When macrophages were preincubated for 3 h with dexamethasone at concentra-tions of 0.01, 0.1 and l μg/ml, thapsigargin (30 ng/ ml) -stimulated PAF production in the cells at 10 min were decreased. However, the maximum inhibition was about 50% even at 1μg/ml of dexamethasone. These date suggest that by treatment with thapsigargin, PAF is partly produced through formation of lyso-PAF by activated phospholipase A₂ since dexamethasone shows partial inhibition of thapsigargin-induced PAF production, and thap-sigargin-stimulated PAF production may partly account for proinflammatory activity of thapsigar-gin.

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Nimesulide (NIM) is a newly developed compound from sulfonanilides, and has been proven to have potent anti-inflammatory and analgesic effects in animal models. These pharmacological effects of NIM are comparable to or more than those of nonsteroidal anti-inflammatory drugs (NSAIDs) . However, NIM affects inhibition of prostaglandin synthetase in vitro quite a little, which suggests that the anti-inflammatory effects shown by NIM may be achieved through the mechanism other than the inhibition of prostaglandin cascade. We studied the effect of NIM on murine collagen-induced arthritis, and investigated whether NIM has antirheumatic effect or not. Type II collagen-induced arthritis was generated in DBA/1J mice. Mice were immunized with a series of subcutaneous injections of type II collagen with complete Freund's adjuvant.
We observed and scored the arthritis, and the serum titers of anti-type II collagen antibody were evaluated by ELISA. NIM or control drugs were administered orally 3 times a week. NIM (1 mg/kg) suppressed not only the incidence and the severity of the arthritis but also the production of anti-type II collagen antibody, whereas indomethacin (3 mg/kg) failed to suppress the antibody production.
These data suggest that the suppressive effect on murine arthritis by NIM may be accomplished through the suppression of immunological events to type II collagen

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There are some papers which report the increase of γδT lymphocytes in peripheral blood of the patients with Behçet's disease (BD) . However, there is no study which reports the analysis of infiltrated γδT lymphocytes in local tissue.
In this study the number of γδT lymphocytes and other T lymphocytes which infiltrated into large intestine of BD patients were counted using im-munoperoxidase staining. The results were compared with other inflammatory bowel diseases and normal controls. In BD the number of T lymphocytes increased in both intraepithelium and lamina propria. However, the ratio of γδT lymphocytes to CD3 lymphocytes decreased in the intraepithelium, while they increse in the lamina propria.
On the contrary, in ulcerative colitis and Crohon's disease, the number of T lymphocytes decrease in the intraepithelium, while they increase in the lamina propria. The proportion of γδT lymphocytes was the same as intestinal BD. The decreased ratio of γδT lymphocytes in BD large intestine might disturb the immunological surveillance and competence and play an important role in the pathogenesis of intestinal BD. The increased number of T lymphocytes in the intraepithelium seems to reflects the increase of αβT lymphocytes and this is the characteristics of intestinal BD.

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Deterpens (plaunotol, gefarnate and teprenone) and isoprenyl chalcone derivatives of sofalcone have been extensively employed as a gastric protective agents. The role of these drugs in cytoprotec-tion have been reported, e. g. mucous secretion, macromolecular synthesis, gastric blood flow, bicarbonate secretion and newly formed capillaries and granulation tissue. Furthermore, it is recently indicated that these gastric protective agents promote increase of the migration of fibroblast and epithelial cells. Accordingly, we investigated the accelerating effect of topical preparation of gastric protective agents on healing of ducubitus and skin ulcers caused by vasculitis. Each topical preparation contained same dosage as orally administration dosage and was once a daily administered to ulcerative lesion.
In 20 cases of patients with intractable decubitus, the wound area was significantly reduced within 1 week and re-epithelization of the ulcer edge and the increase of granulation tissue were also observed in 2 weeks after treatment. Healing acceleration rate by these drugs were about the same. In cases of patients with skin ulcers, healing acceleration was also comfirmed.
These results suggest that topical preparation of gastric protective agents are useful for the treatment of wound healing.

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Urinary trypsin inhibitor (UTI) is a glycoprotein which is excreted in human urine, and an inhibitor to multiple enzymes. In recent years, UTI has been recognized to be one of acute phase reactants in cases of infection and so on, because the amount of UTI excreted in urine increases or decreases in concentration in parallel with those of serum CRP and/or erythrocyte sedimentation rate, etc. However, study on UTI so far in the area of pediatrics is rare, so, we examined in 66 cases of children suffering from infection.
In this report, 13.6% of false negative cases were observed with respect to CRP. The amount of UTI was found to increase in the early days as serum CRP, and UTI moved to decrease in parallel with that of CRP when the diseases became getting well. Moreover, the ratio of UTI values between admission and discharge was proved almost equal to that of CRP.
The results suggested the immunological assay of UTI is sensitive and useful to detect and monitor the course of infections as well as CRP. Because of less invasive method, that is, urine is sample, routine assay of UTI would be desired.

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The effects of roxithromycin, a new orally semisynthetic macrolide, were investigated on human neutrophil chemotaxis and phagocytosis in vitro. The agent markedly stimulated neutrophil chemotaxis and phagocytosis in a dose-dependent manner. These results may indicate that roxith-romycin potentiates the activation of neutrophils in vivo.

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Bucillamine (1.6-3.0 mg/kg/day) was administered to 9 children with rheumatic diseases resistant to aspirin. The usefulness was evaluated based on improvement in the functional impairments and other symptoms at 12 weeks and 1 year after administration.
The results disclosed evidence that clinical improvement with decreased numbers of painfull joints in 7 cases (5 cases with polyarticular type JRA, 1 case with juvenile chronic arthritis and 1 case with spondyloarthropathy) . Stomatitis was found in 2 cases and proteinurea in 1 case as adverse effects.
Bucillamine was useful for children with rheumatic diseases to whom nonsteroidal antiinflammatory drug was ineffective.

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