A cardinal feature of inflammatory reaction is the leukocyte infiltration in the foci, and particular interests are whether the motile cells present in the blood are attracted to inflamed spots and if so what chemical substances produce the effect. In vitro experiments has been revealed that may substances are chemotactic for macrophages and lymphocytes. However, the relative importance of these factors in the in vivo reaction is far from clear. The possible importance of leukocyte chemotaxis in inflammation is highlightened by the discovery of chemotactic factors for macrophages and lympocytes in the inflammatory sites. At least four factors, plasma-derived, IgG-derived, lymphokine, and C5a, for macrophages, and four factors for lymphocytes; are found in vivo sites. The relative activity of the factors are different with the age and type of inflammation. Macrophages, thus emigrated into inflammatory foci, appears to play roles a) as an accessory cells for immunological responses, and b) as an effector cells for inflammatory processes. Emphasis is paid to the secretory activities of macrophages. They produce and release many active substances for inflammation, host defence and regulation of function of other cells. Lymphocytes play roles a) directly as an cytotoxic effector cells, and b) indirectly as secretory cells of chemical substances in and around the site of injury. The whole question of chemotaxis of leukocytes in inflammation and the role of these cells in inflammatory lesions are still premature but are extremely active and rapidly moving area of investigation, and “attracts” many of the investigators.

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This study showed the affection of prostaglandins (PG) on the in vitro IgG, IgM production by pokeweed mitogen stimulated normal human peripheral blood lymphocytes. Concentrations of PGE₁ and PGA₁ in excess of 10^-6 M were suppressive. PGE₂ and PGs of the F series were less suppressive and significant suppression was seen in concentrations greater than 10^-5 M. Indomethacin added to cell cultures did not enhance Ig production. This discrepancy between physiologic concentrations and the very large pharmacologic concentration necessary to suppress Ig synthesis in vitro makes the physiologic role of PG in the modulation of Ig synthesis questionable.

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The effects of prostaglandins on human polymorphonuclear leukocytes (PMN) migration were studied in vitro by agarose plate method. None of the prostaglandins tested, including PGE₁, E₂, F_2α and thromboxane B₂ (TxB₂) were chemotactic in concentrations ranging from 0.5 to 10 μg. However, pretreatment of PMN with PGE₁ and PGF_2α for 30 minutes at 0°C inhibited the chemotaxis induced by zymosan activated human serum as well as spontaneous migration of PMN, while pretreatment with TxB₂ enhanced these reactions. These findings suggested that in some forms of inflammation, prostaglandins may play a controlling role in leukocytes migration. The inhibition or enhancement of PMN migration was not directly related to the changes of intracellular cyclic AMP levels by prostaglandins.

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Kinetics of inflammatory cell accumulation in mice in response to glycogen and influence of protease inhibitors and anti-inflammatory drugs were studied. Leukocytes in blood maximally increased at 2 hr after glycogen injection. The maximum cell accumulation in the peritoneal cavity was observed at 8 hr, whereas the protein content in the peritoneal exudate reached the maximum level at 1-2 hr and then decreased. Among drugs examined, indomethacin and dexamethasone suppressed markedly the accumulation of white cells and protein exudation.

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The values of plasma 6-keto-PGF_1α, metabolite of prostacyclin and basal level of platelet prostanoids were measured by RIA, before and during PGE₁ administration and just after and one week after completion of the treatment to seven collagen disease patients (2 cases of PSS, 1 case of SLE, MRA, Behçet, PN and MCTD) and 2 cases of Buerger's disease and 6 cases of diabetes mellitus as the control of non-inflammatory diseases, and the following results were obtained: 6-Keto-PGF_1α values in plasma and both iPGE values and E/F ratio in platelet suspensions were decreased significantlly just after and one week after completion of PGE₁ treatment, in both collagen disease patients and control subjects. These results indicate that the clinical effect of PGE₁ treatment in peripheral vascular diseases may result from improvements of both hypoxia in organs and hyperaggreable state of platelet.

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Vascular changes in Behçet's disease are important in not only vasculo-Behçet's disease, but also the most cases. Thrombo-phlebitis of cutaneous vein frequently and that of deep vein occasionally are found. We experienced two cases of Behçet's disease with hyperplatelet aggregation. In the first case, we observed multiple thrombosis of deep vein including vena cava and subclavia. The second patient was admitted because of cerebro-vascular disorders. The platelet aggregation induced by ADP markedly increased in both cases. We also observed a tendency of hyperplatelet aggregation in another 9 cases of Behçet's disease. We used fenbufen and dipyridamole, anti-thrombocytic drugs to our patient. The hyper-aggregation decreased and turned almost normal after the treatment. Thus, we think that the use of anti-thrombocytic drugs may benefit certain patients with Behçet's disease by inhibiting thrombostic events.

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The purpose of this paper is to show under what clinical setting the patients with SLE have systemic vascular lesions. Thirty-four autopsied cases with SLE were used as subject materials of this study. SLE patients with thrombosis had myocarditis and convulsions significantly more than the patients with other histological vascular lesions. The causes of death for patients with vascular fibrinoid degeneration and thrombosis was mainly uremia; on the contrary, death of patients with vascular sclerosis was more often caused by infection. The patients with thrombosis and vascular sclerosis had Libman-Sacks endocarditis significantly more than the patients without the systemic vascular lesions. The patients with involvement of the mediumsized artery had a low female incidence, photosensitivity incidence and positive LE cell incidence, and the cause of death for these patients was cerebral vascular involvement more than the patients with small artery involvement and those without systemic vascular lesions. One patient with vascular sclerotic involvement of the me-dium-sized artery died of myocardial infarction. From the point of view of systemic vascular lesions in SLE, the prognosis of the patients with thrombosis and vascular involvement of medium-sized arteries was the most severe.

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Gastrointestinal absorption of CS-600 was shown to be rapid and almost quantitative in rats. The cyclopentanone moiety of CS-600 was reduced rapidly to afford a mixture of trans-OH and cis-OH as principal metabolites in plasma of rats, dogs and monkeys. The plasma levels of trans-OH having strong inhibitory activity for PG synthetases was 2-3 times higher than that of cis-OH. The stereochemistry of trans-OH isolated from rat urine was established to be a single SRS-configuration, indicating the stereospecific reduction of the cyclopentanone moiety. The CS-600 reducing enzyme was purified from rabbit liver cytosol fraction as single protein and shown to be one of the aromatic aldehyde-ketone reductases on the basis of substrate specificity, effects of inhibitors, optimal pH (6.2), cofactor requirement (NADPH) and molecular weight (ca. 33, 000) .

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CCA {disodium 4-chloro-2, 2'-imminodibenzoate} is a new compound synthesized and developed by Chugai Pharmaceutical Co., Ltd. CCA has been suggested to have an immuno modulating effect in animals. In this paper, we presented the effect of CCA on the PFC and RFC (rosette forming cell) response for SRBC in vivo. We have already reported that the immunoresponse in C₃H/He mice decreased with the age. In this experiment, we used aged C₃H/He mice and found that the number of PFC and RFC in the aged C₃H/He mice was increased by the treatment of CCA. This results suggest that the decreased immunoresponse in the mice was recovered to normal level by CCA treatment.

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It was found that CCA shows slight prophylactic and therapeutic effects on the secondary inflammation of rat adjuvant arthritis while it does not on the primary inflammatin. The therapeutic effect of CCA was characterized by its improving effect on the arthritic score when administered from day 21 to day 50 after adjuvant injection. The effect in this case was almost comparable to those of other anti-inflammatory drugs such as flufenamic acid, indomethacin or prednisolone. The mechanism of CCA upon rat adjuvant arthritis is different from those of known anti-inflammatory drugs and was assumed to be due to its immuno-modulating action.

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