When normal leukocytes, especially neutrophils, are stimulated by various stimuli, such as opsonized zymosan, opsonized bacteria and phorbol myristate acetate etc, they produce O^-⋅₂ (superoxide) from O₂ by the catalytic action of NADPH oxidase systems present in their plasma membrane. Superoxide is not a powerful oxidant and easily converted to H₂O₂ by the dismutation of 2O^-⋅₂. Hydrogen peroxide itself is not a oxidant in aqueous media, but can be converted to powerful oxidants, one for ⋅OH and another for HOCl in neutrophils. The most plausible way for the generation of ⋅OH in the leukocytes is the reaction of H₂O₂ with Fe²⁺ (Fenton's reaction) . Ferrous ion could be supplied by the redution of Fe₃₊ by O^-⋅₂ (probably also by ascorbate) . Such ⋅OH generating system is extensively important for killing bacteria in myeloperoxidase-deficient leukocytes. The generation of HOCI from H₂O₂ is catalyzed by myeloperoxidase in neutrophils in the presence of CI^-. Bacterial membrane and energy-producing system are strongly damaged by HOCI (probably also by ⋅OH) . Of the active oxygen species, ¹O₂ may also be produced during dismutation of O^-⋅₂ and by the reaction of H₂O₂ with ^-OCI at neutral pH, but in a very small quantity. Judging from very short lifetime and very selective reactivity of ¹O₂ to organic compounds, it seems unlikely that ¹O₂ is an active species for killing bacteria. The mechanism of luminol-dependent chemiluminescence produced by activated leukocytes is also discussed in this review.

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The role of IgG₄ antibodies in immediate hypersensitivity will be discussed in this paper, both from experimental and clinical point of view. The data described will show that 1) not only IgE but also IgG₄ molecules are present on human basophils, 2) IgE-mediated basophil degranulation may be inhibited by passive sensitization with excess amounts of IgG₄ antibodies, 3) allergen-specific IgG₄ antibodies become prominent upon repeated parenteral stimulation with antigen, such as immunotherapy and bee-stings, in asthmatics and in bee keepers. The overall results suggest that IgG₄ antibodies may react as blocking antibodies which produce protective effect during clinical course, in a certain type of allergic disorders. The role of IgG₄ antibodies as anaphylactic antibodies will be also briefly discussed.

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It has been elucidated that phagocyte-released oxygen intermediates (O^-₂, H₂O₂, OH⋅, ¹O₂) (OI) which are excessively generated to fuse invading agents in their phagosomes induce auto-oxidative damage such as tissue injury in several human cells in vivo. On the other hand, superoxide dismutase (SOD), oxygen-scavenging enzyme is produced in every human cell to prevent itself from auto-oxidative damage by increasingly released OI. Recently, there have been reports suggesting the auto-oxidative damage only from the result of a decrease in SOD activity. In this study, the authors assessed both the capacity for generating OI by neutrophils and SOD activity in blood including serum and blood cells of the patients with various diseases to calculate OI/SOD ratio, by which tissue injury induced by an increase in OI in every disease was investigated and discussed. Patients with dermatitis herpetiformis in whom both an increase in OI generation and a decrease in SOD activity were found, showed the highest OI/SOD ratio. The patients with mucocutano lymphnode syndrome (within 5 days after onset) and rheumatoid arthritis (but only in synovia) in whom an increase of OI generation was not accompanied by that of SOD activity, showed nextly high OI/SOD ratio. In the cases of active Behcet's disease, severe cement dermatitis and untreated, active SLE with similar behaviours, the ratio was also elevated. Since in these patients, marked tissue injury has been reported to be found, the present study revealed that the examination of the difference between OI levels and SOD activity is closely related to the tissue injury analysis.
In the patients with bacterial infections an increase of both OI generation and SOD activity was observed. And the cases of viral infections and various cancers showed a slight decrease of both OI production and SOD activity. In the patients with these three disorders, OI/SOD ratio was within normal levels. Asymptomatic heavy smokers with more than 40 pieces of cigarettes a day for 20 years of longer showed a remarkable increase in OI generation sufficiently accompanied by enhanced SOD activity. However, two cases which had been considered to be asymptomatic but were revealed lung cancer 7-10 months later, had not shown an increase in SOD activity, leading to a markedly elevated ratio of OI/SOD. OI/SOD ratio which the authors proposed in this study seems to work as an indicator of tissue injury induced by increasingly produced OI and further possibly predict the asymptomatic individuals in pre-cancer stage.

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A5μg/kg, p.o, dose of prostaglandin E₂ (PGE₂) was given to male Donryu rats (each weighing about 180g) prior to water immersion. As compared with the untreated control, PGE₂ markedly decreased the incidence of water immersion-induced ulcers. This study suggested that PGE₂ might stabilize the activities of glandular kallikrein, tissue plasminogen activator and endogenous prostaglandin E. PGE₂ was furthermore shown to increase the production of acid mucopolysaccharides (AMPS), especially a total of heparan sulfate (HS), and chondroitin sulfate A, B and C (CS-A, -B, and -C) . Then, the effect of HS, CS-A, CS-B and CS-C on arachidonic acid, collgen and thrombin-induced platelet aggregation in the presence of antithrombin III (AT-III) was investigated by using human platelet-rich plasma. Although arachidonic acid and collagen-induced platelet aggregation was not inhibited by any of these AMPS fractions, only thrombin-induced platelet aggregation was inhibited by the heparin-like effect of HS, CS-A and CS-B. The effect of PGE₂ (5μg/kg, p.o.) given prior to the intra-arterial administration of dl-norepinephrine (1μg/kg) was also investigated using Donryu rats. Biomicroscopy showed that PGE₂ effectively protected the gastric mucosa against dl-norepinephrine-induced stress, widening the caliber of capillaries and keeping a constant rate of blood flow.

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It is held that jaw cysts enlarge as the bone is absorped because of the intracystic fluid pressure. It is also held that the cysts enlarge as prostaglandin-like substances of the cyst walls acts on the bone resorption. This study gave the following results. As the concentrations of PGE generated in infected cyst walls increased, bone Gla protein, and calcification decreased and the bone was absorpted. After the infection of the cyst disappeared, the value of PGF₂α, bone Gla protein, and calcification increased, and the bone regenerated

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Auranofin, an oral gold compound, was administered 3 mg twice daily to twenty-eight patients with classical rheumatoid arthritis (3 men, 25 women) who had developed undesirable reactions (mostly mucocutaneous in nature) against gold sodium thiomalate (GST: 24 cases) or D-penicillamine (D-Pc: 4 cases) during the previous 6 months. 19 cases (17 on GST and 2 on D-Pc previously) completed the full 24 weeks' study. Because of the recurrent dermatitis, five patients, 3 of whom had been on GST, were withdrawn from the trial during the initial eight weeks. Four other patients who had all taken GST previously, dropped out of the study because of intervention of other diseases (2 cases), failure to respond (one case) or not returned (one case) . Among the nineteen patients who had been on GST before and managed to take Auranofin over the initial 12 weeks, seven (36.8%) showed positive clinical response, while 3 (15.8%) deteriorated slightly. Those who had been managed substantially well by GST, seemed to have better prognostification to the following oral gold treatment. As for the D-Pc cases, no definite conclusion was reached, because very limited number of cases was available for the study.

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Lobenzarit disodium (CCA; disodium 4-chloro-2, 2'-iminodibenzoate) had no inhibitory effect on carrageenan eodema, cotton pellet granulomatosis, acetic acid writhing test, hot plate test and passive cutaneous anaphylaxis reaction. CCA also did not show an inhibitionin vitroPGE₂biosynthesis. These results clearly show that CCA is quite different from mefenamic acid in its biological activities while the chemical structures of both are similar. The suppressive and inhibitory effects of CCA on the immunologically-induced murine inflammation such as adjuvant arthritis and methylated bovine serum albumin-induced arthritis in rats or spontaneously occurred autoimmune diseases in NZB/NZW F₁and MRL/1 mice, were thought to be derived from its immunomodulating activity.

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Previous findings have suggested that the therapeutic effect of lobenzarit disodium (CCA) on adjuvant arthritis in rats is based on its immunomodulating activities. Studies in this paper showed that CCA had no therapeutic effect in arthritic rats which were depleted of T lymphocytes by means of such as the injection of anti-thymocyte serum and adult thymectomy. This strongly suggests that CCA exerts its anti-arthritic effect through the activation of suppressor T lymphocytes.

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慢性関節リウマチ患者6人を対象として, NK-19 100μgを2～17ヵ月連日投与し, その効果, 認容性および免疫学的パラメーターについて検討した.
(1) 最終全般改善度は, 改善1例 (17%) , やや改善4例 (67%) , 悪化1例 (17%) となった.
(2) 最終全般改善度と相応したLansbury's indcxの改善が認められたが, 改善を示した評価項目には一定の傾向は認められなかった.
(3) RAテストおよびRAHAが改善する症例があったが, immunoglobulin, 抗核抗体など他の免疫学的パラメーターの変動は認められなかった.
(4) T cellおよびB cellの著明な減少傾向が認められたが, IgG-FCR (Tγ) の変動はみられなかった.またPHAおよびConAによるリンパ球幼若化反応もまた変動は認められなかった.
(5) 副作用および随伴症状はまったく認められず, また一般臨床検査の異常も認められなかった.

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