Chiyuki Abe

Association between HLA and Japanese patients with rheumatoid arthritis.

Japanese patients with rheumatoid arthritis (RA) were observed to have a statistical association with HLA-DR4, MT3. Strong association between the clinical severity of RA and HLA was also observed. Male patients had a stronger association with HLA than female patients. Males are more resistant to RA than females. This suggested that the threshold of liability for RA is higher in males than in females. Japanese patients with RA with systemic vasculitis were negative for HLA-Bw44 and had antilymphocytotoxic autoantibody, indicating that RA with systemic vasculitis is different in etiology from RA without systemic vasculitis.

Effects of immunomodulators on candidacidal activity of normal peritoneal cells in BALB/c mice

Macrophages which play an important role in host resistance against infections are considered to be a target for various immunomodulators. In order to examine the effects of selected immunomodulators on macrophage function, the effects of N-(2-mercapto-2-methylpropanoyl)-L-cysteine (SA96), levamisole (LMS) and D-penicillamine (D-Pc) on the candidacidal activity of the normal peritoneal cells (PC) were investigated. In the in vitro studies, SA96 increased the candidacidal activity of PC 4-fold, while D-Pc and LMS treatments did not increase this activity. In the ex vivo studies, PC obtained from the mice pre-treated with SA96, D-Pc and LMS showed a high candidacidal activity. Elevated candidacidal activity was not due to changes of cell types of PC populations. These results suggest that D-Pc and LMS activate the function of macrophage in vivo and SA96 activates the function both in vitro and in vivo.

Immunomodulation by RS-2131, a new non-steroidal antiinflammatory drug

The immunomodulatory properties of RS-2131, 2-[4-(2-oxocyclohexylidenemethyl)phenyl]propionic acid, were studied using normal and autoimmune mice. RS-2131 suppressed the Arthus-type footpad reaction in BALB/c mice when administered orally at the time of immunization with sheep red blood cells, in contrast to indomethacin. This drug also suppressed the direct plaque-forming cell response against sheep erythrocytes in BALB/c mice. Under the same experimental conditions, the percentage ratio of Lyt 2+ cells to Thy 1.2+ cells were increased in the spleen cells. When used in non-immunized normal BALB/c mice, however, RS-2131 produced no effect on the ratio of Lyt 2+ cells to Thy 1.2+ cells in the spleen cells and on the percent distribution of T lymphocyte subsets. In MRL/Mp-lpr/lpr (MRL/lpr) mice, which have been known as a model of autoimmune disease, Lyt 2 cells in the thymus and the lymph node increased on oral treatment with RS-2131. These findings suggest that this drug may induce suppressor T cells only when the immune response in host animals is increased and then results in inhibition of immune responses in mice.

Correlation of natural antibodies to nuclear substances in New Zealand and other strains of mouse

Abstract Female mice of seven strains were studied at 3, 6, and 8 months of age for the presence of spontaneously occurring antinuclear antibodies (ANA), anti-double-stranded RNA (dsRNA) antibody and anti-single-stranded DNA (ssDNA) antibody. It was demonstrated in this report that ANA does not necessarily correlate with the presence of anti-dsRNA antibody and anti-ssDNA antibody, C57Bl and (NZB × AKR)F1 had no ANA or antibodies to the nucleic acids. CBA H mice had positive anti-dsRNA antibody at each age studied. SJL J and AKR mice, strains with a high incidence of spontaneous neoplasia, had ANA at 6 and 8 months ( SJL J ) and anti-dsRNA antibody at 6 months (AKR). NZB and (NZB × NZW)F1 mice which spontaneously develop autoimmune disease had positive ANA and high titer of antibodies to dsRNA and ssDNA. ssDNA was found to be the most discriminative antigen for autoimmune disease of NZB or (NZB × NZW)F1 mice.

Effects of immunomodulators on the four types of hypersensitivity

In the textbooks of immunology, immune reactions were described in 5 types of allergic or hypersensitivity reaction, i.e. I (anaphylactic), II (antibody-dependent cytotoxic), III (complexmediated), IV (cell-mediated or delayed), and V (stimulatory) . Antigen and antibody involved, reaction time, histopathological characteristics, clinicl test, disease examples are also weiten in each type respectively.Immunopharmacology is a newly developed science and progressed rapidly as immunology did. Many investigators are analyzing effects of the drugs on each immune responsive cell. Immunomodulators are understood to possess suppressive effect on hyperimmunity state, augmentative effect on hypoimmunity state, and no effect on normal immune state. Thymostimulin (TP-1), and thymopoietin (TP-5), as thymic hormones; levamisole (LMS), D-penicillamine (D-Pc), mercapto-methylpropanoyl cystein (SA-96), gold salt thiomalate (GST), and auranofin, as SH compounds; carboxyphenyl chloroanthranilic acid (CCA), traxanox, and methyocobalamin (CH3B12), as others; were discussed in this report immunopharmacologically. No paper had described relationship between immunomodulators and 5 types of hypersensitivity reaction. The drugs had suppressive or augmentative or no effect on the 4 types (I, II, III, IV) of hypersensitivity. The effects might not be the yield of single immune responsive cell but the result of the reactions of several immune responsive cells in the respective types of reaction.Analysis of effects of the immunomodulators on the different types of hypersensitivity reaction possibly elucidate the mechanism of the drugs and diseases to be applied.

Effects of water-soluble adjuvant (WSA) on New Zealand (NZB × NZW) F1 hybrid mice

Water-soluble adjuvant (WSA) extract of Mycobacterium smegmatis is a noncytotoxic adjuvant which boosts antibody formation to exogenous antigens in mice. If the hyper-responsiveness of New Zealand (NZB × NZW)F1 hybrid (B/W) mice is due to the adjuvant activity of endogenous nucleic acids, their disease would be expected to accelerate after administration of adjuvant which lacks nuclear substances. WSA did not accelerate or decelerate the nephritis of the B/W mice, but it did decrease significantly the hepatic retention of exogenous single strand DNA (ssDNA). The simultaneous injection of WSA and ssDNA in B/W mice resulted in less hepatic retention of 125I-labeled ssDNA and delayed progression of the glomerulonephritis. Mice which received either ssDNA or Freunds complete adjuvant had accelerated lupus nephritis without an apparent increase of antibody formation to nuclear substances. We therefore suggest that the immunologic hyper-responsiveness of B/W mice might be caused by effects other than adjuvanticity of nuclear substances. The autoimmune disease of these mice seems to be multifactorial, requiring at least the presence of immunogen, genetic factors, and perhaps other agents or mechanisms.