Anti-inflammatory mechanism of inflamed-tissue factor
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The early postulation that irritation of tissue could release a substance which acted as anti-inflammatory agent at a remote site of the body, led further to show that administration of inflammatory exudate results in suppression of experimental inflammations (Rindani , Robinson and Robson , Billingham, Robinson and Robson , Bonta and De Vos ). Little is known however as to which type of inflammatory response is preferentially inhibited by inflammed-tissue factors(s) and even less is known the mechanism associated with this inhibition. Earlier we studied the anti-inflammatory effect of exudates from peritoneal inflammation, but in later experiments we made use of exudates obtained from aircarrageenin granuloma pouches of rats (Bonta, Bhargava and De Vos ). The dialysate of the exudate showed only potency in suppressing the kaolin induced hind paw inflammation of the rat. A marked and dose dependent inhibition of this inflammation was however found with the retentate. The anti-inflammatory macromolecular (mol wt 200,000) portion of the exudate is a complexity of proteins and may be other materials. The macromolecular factor(s) obtained from donor rats did also suppress the kaolin induced hind paw inflammation when administered to mice, herewith ruling out species-specificity. The anti-inflammatory effect of the exudate was not diminished by adrenalectomy of the test-animals, thus excluding the discharge of corticosteroids as a conceivable mechanism. The macromolecular retentate did not only cause inhibition of the kaolin induced inflammation, but the carrageenin-inflammation in rats was also suppressed. On the other hand the inflammatory response by histamine or serotonin was not inhibited by the pouch-exudate, which thus apparently displays a preferential inhibition of certain type of inflammations while leaving others unaffected (Bonta, Bhargava and De Vos ). We found no indications that the anti-inflammatory effect of the exudate factor(s) was mediated through either influencing the kininogen-kinin system or interfering with prostaglandins as putative inflammatory mediators. However depletion of complement was evident in the carrageenin induced inflammation, representing the type of response which is sensitive to the anti-inflammatory effect by the pouchexudate. In line with this we have data that the exudate inhibits total complement activity of serum when either added in vitro or administered in vivo. The complement inhibitory property of the exudate seemed to parallel with the anti-inflammatory activity. Complement fixation has been proposed as the underlying mechanism of the counterirritant principle (Willoughby, Coote and Turk ), which in fact was the early starting point to investigate the anti-inflammatory effect of exudates obtained from irritated tissue. It is however, not likely that tissue irritation due to injection of our macromolecular factor is the exclusive mode in its anti-inflammatory effect. In fact we observed the anti-inflammatory effect even after intravenous administration, which largely rules out local tissue irritation. Complement inhibition appears to be a common pathway in the anti-inflammatory effect of the counter-irritant principle and of inflammed-tissue factor(s). The latter may however induce this effect without counter-irritation. Furthermore complement inhibition does not exclude the participation of other conceivable mechanisms (e.g. lysosomal membrane stabilization) in the anti-inflammatory effect of the inflamed-tissue exudate, which most likely contains more than one active factor.
KeywordsKaolin Dose Dependent Inhibition Lysosomal Membrane Complement Fixation Conceivable Mechanism
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