Rheumatoid arthritis (RA) is a chronic inflammatory disease of joint synovium. Several cytokines, including TNF alpha, IL 1, GM-CSF, IL 6, IL 8, MCAF/MCP-1, PDGF, and TGF beta have been detected in joint tissue as well as in synovial fluids from joint of RA. Possible roles of these cytokines in controlling pathophysiological state of RA joints was extensively discussed in this review article.

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Docosahexaenoic acid (22 : 6ω3, DHA), a major polyunsaturated fatty acid of fish oils, is found in retina, sperm, heart of land animals, as the major fatty acid component in phospholipids. DHA is probably essential for the functional development of nervous system including retina. DHA is reported to modulate arachidonic acid metabolism, and to have anti-inflammatory effects. It is also reported that DHA has many other effects such as depression of platelet aggregation, augmentation of the efficacy of anti-cancer drugs, prevention of arrhythmia and reduction of serum cholesterol. Consequently, DHA administration is expected to be useful for various diseases.

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Lipid peroxidation and its anticancer effect induced by gamma-linolenic acid and iron (GLA+Fe) were studied by ultraviolet-spectrophotometric (UV) and gas chromatographic-mass spectrometric (GC-MS) methods. When both were supplemented with GLA +Fe, there were far more dead cells in human breast cancer (ZR-75-1) cultures than in human normal skin fibroblasts (CCD 41-Sk) . Accelerated lipid peroxidation was confirmed by the formation of conjugated dienes (CD) in the polyunsaturated fatty acids (PUFAs) and by the formation of hydroperoxyl group (OOH) indicated by the conversion of triphenylphosphine (TPP) to its oxide (TPPO) only in ZR-75-1 cells but not in CCD 41-Sk cells treated with GLA+Fe. Vitamin E inhibited the enhancement of peroxidation and cell killing produced by Fe in ZR-75-1 cells. It was shown that an accelerated production of lipid peroxides detected as CD and OOH-TPP reaction in cancer cells (ZR-75-1) was closely associated with the cancer cell killing produced by GLA+Fe.
These findings suggest a lipid peroxidation mechanism specific to malignant cells to be investigated further, which might open the possibility of applying PUFA such as GLA as a highly selective antineoplastic agent and a sensitive reagent to detect malignancy.

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Active oxygens production in human monocyte was evaluated using two fluorescence probes, 2', 7'-dichlorofluorescin diacetate (DCFH-DA) and the anti-CD11c monoclonal antibody conjugated phycoerythrin (PE), on condition that the influence of neutrophil and plasma was removed. As results, in case of PMA stimulus, the active oxygens production of the inflammation and cancer disease has heightened significantly in comparison with the healthy controls. But, in case of phagocytic stimulus by opsonized zymosan, there was not a significant difference. This suggested that the decline of phagocytic function in monocyte of these diseases was reflected about the active oxygens production by phagocytic stimulus.
We investigated about the influence of metabolites of arachidonic acid on the reaction system. As results, it was showed that there was not a influence of prostaglandin (PG), but it was not clear about a influence of leukotriene (LT) . Then, it was showed that the active oxygens production decreased remarkably by addition of plasma in the reaction system.

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Employing the air pouch-type allergic inflammation model in rats, effects of inflammatory exudate on histamine production by bone marrow cells were examined in order to clarify the mechanism of histamine production at the site of allergic inflammation. The pouch fluid collected 8 h after the induction of allergic inflammation (the acute phase) increased histamine production by bone marrow cells. On the other hand, the pouch fluid collected 5 days after the antigen challenge (the chronic phase) showed no activity by itself, but enhanced the activity by the pouch fluid collected at the acute phase. These activities were due to proteinous factors that were produced at the acute phase and at the chronic phase, named histamine-production-increasing factor (HPIF) -I and HPIF-II, respectively. HPIF-I increased histidine decarboxylase (HDC) activity in bone marrow cells but HPIF-II did not. However, HPIF-II enhanced HDC activity stimulated by HPIF-I. The cooperative effect of HPIF-I and HPIF-II on histamine production was also observed in vivo. Isoelectric point and molecular weight of HPIF-II were estimated to be 7 to 8 and about 100 kD, respectively.
These results indicate that histamine production at the site of allergic inflammation might be regulated by at least two kinds of proteinous factors, HPIF-I and HPIF-II.

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Monocrotaline (MCT) causes lung inflammation and chronic pulmonary hypertension in rats. We hypothesized that platelet-activating factor (PAF) might play a role in MCT-induced pulmonary hypertension, and measured PAF levels in lung tissue of MCT-treated rats. Then, we examined the effect of specific PAF-antagonists, WEB 2086 and WEB 2170, on MCT-induced pulmonary hypertension and right ventricular hypertrophy. The PAF levels in the lung tissue increased at 1 and 3 weeks after MCT-injection. Treatment with WEB 2086 or WEB 2170 significantly reduced pulmonary hypertension and right ventricular hypertrophy induced by MCT at 3 weeks after injection.
These results indicate that PAF-antagonists inhibit the development of pulmonary hypertension induced by MCT. We conclude that PAF contributes to the development of pulmonary hypertension induced by MCT in rats.

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A new multi-well assembly was used for the in vitro chemotaxis assay of human peripheral blood monocytes. N-formylmethionyl-leucyl-phenylalanine caused concentration-dependent migration of the monocyte into the lower surface of the metal flamed membrane filter. Measurement was performed by the microplate reader (550-600 nm), and the absorbance showed the complete dependence on the number of migrated cells.

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The effects of four different average molecular weights (MW) ; 0.47, 0.95, 1.52 and 2.0 × 10⁶, respectively of sodium hyaluronate (HA) designated those each as HA-47, HA-95, HA-152 and SL-1010, on the neutrophil functions including chemotaxis, adhesion to the plastic plate, phagocytosis and superoxide generation, and expression of CD44 antigen were studied.
The inhibitory effect of HA on neutrophil chemotaxis was found to be dose (0.1-0.4 mg/ml) - and MW (0.47-2.0×10⁶) -dependent. Neutrophils were also observed to be inhibited to adhere to a plastic plate when the cells were treated with 10 μg/ml each type of HA. However, only SL-1010 inhibited the cell adhesion at the concentration of 1 μg/ml. Phagocytosis of FITC-latex particles was also found significantly inhibited by the HA-152 and SL-1010, but not by the HA-47 and the HA-95 at the concentration of 1 mg/ml. These inhibitory effects on the chemotaxis and phagocytosis observed in the presence of HA were similarly observed when neutrophils were pretreated with and washed out SL 1010.
The generation of superoxide anions by stimulation with opsonized zymosan (OZ) was inhibited by the addition of HA, and this effect was also found to be dose- and MW-dependent.
The effect of HA on neutrophil activating antigen, CD44 was analysed after the stimulation with OZ, and the results revealed that the CD44 expression on neutrophil was down-regulated by the stimulation. The down-regulation of CD44 was inhibited by HA in a MW-dependent manner.
These results indicated that HA, especially the high MW SL-1010 might be a modulator against the activation of neutrophil to the inflammatory cascade.

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A new cyclosporin A (CSA) ointment was prepared and its effect on contact skin reactions was evaluated in guinea pigs. 0.1% or 0.5% dinitrofluorobenzene (DNFB) -induced contact skin reactions were inhibited by twice daily topical application of 1-10% CSA ointment preparation, which showed more potency as compared to those of other topical CSA's or steroids. In contrast to oral administration of CSA (50 mg/kg) for 4 days, topical application over the same period resulted in more suppressive effect on contact skin reactions with rather lower CSA levels in blood (150 ng/ml) . CSA contents of this preparation were little changed even at 60°C for 3 months.
These results indicate that this new CSA ointment is effective and stable preparation. Moreover, there would be a possibility that this preparation may be valuable in the treatment of human cutaneous immune-mediated disorders.

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In this study, we investigated the pharmacologic effect of topical cyclosporin A (CSA) cintment on skin allograft from Lewis rats to Fischer rats. The 10% CSA ointment was prepared and applicated. Untreated allografts were rejected in 11.0±1.0 days, but long term graft survival (26.3±2.7 days) was significantly seen with continuous topical 10% CSA ointment treatment for 12 days at 15 mg/rat/ day (P<0.001) . The mean survival time of allograft receiving topical 10% CSA ointment was significantly (P<0.05) even longer than the allografts receiving 4 mg/kg/day i.v. for 15 days (21.7±4.4 days) .
Light microscopy revealed the deposition of PAS positive granules in and exfoliation of proximal tubular epithelium in rats receiving topical CSA ointment. These changes were observed likewise in untreated rats. So it may be not characteristic of CSA nephrotoxicity.
These results suggest that topical CSA ointment may play an important role in application of allcgraft to cover skin defects caused by severe burn injury.

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We studied the effects of azelastine and salbutamol on the sulfur dioxide (SO₂) -induced inhibition of airway ciliary motility. Azelastine and salbutamol dose-dependently increased ciliary beat frequency (CBF) of rabbit tracheal epithelium, as detrmined by a photoelectric technique. Perfusate bubbled with 10 ppm SO₂ greatly decreased CBF and intracellular cyclic AMP levels, an effect that was reversed by pretreatment of cells with azelastine and salbntamol.
Thus, azelastine might protect against SO₂-induced airway injury by accumulating cyclic AMP in epithelial cells.

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