Role of nitric oxide in depressed lymphoproliferative responses and altered cytokine production following thermal injury in rats.

Immunodeficiency follows extensive burns. We investigated some underlying mechanisms in rats, 10 days after a full-thickness skin burn affecting 20% of total body surface area. In both normal and burned rats the splenocyte proliferative response to Con A was linearly and negatively correlated with nitric oxide (NO) production. In all burned rats, the proliferative response was depressed by more than 80% and NO production corresponded to a nitrite concentration above 20 microM. Proliferative responses in burned rats were fully restored in the presence of 250 microM NG-monomethyl-L-arginine (NMMA). A time course study of NO production in response to Con A, LPS, anti-CD3, and IFN-gamma showed that splenic macrophages from burned rats responded to direct and indirect stimuli more rapidly and more intensively than normal macrophages. In the second part of this work, the effect of the overproduction of NO on the synthesis of immunoregulatory and proinflammatory cytokines was investigated. Although it was inhibited, IFN-gamma production by splenocytes from burned rats remained sufficient for NO synthase induction and was restored by NMMA. Concomitantly, IL-2 concentration was enhanced but returned to normal in the presence of NMMA. TNF production was halved after burn injury and NMMA partially restored it. In contrast, IL-6 production was enhanced and increased further in the presence of NMMA. Therefore, cytokines were differently affected by burn injury and variously regulated by NO.

Inflammatory reactions induced by various calcium pyrophosphate crystals.

Various inflammatory reactions can be induced by different crystals responsible for various arthropathies. The aim of this work was to study modifications induced in the rat, locally and at distance, by intrapleural injection of 3 forms of pyrophosphate crystals (CaPP dihydrated monoclinic (M), CaPP dihydrated triclinic (T) and CaPP anhydrous (beta]. The data presented here show that the structure of irritants plays a decisive role in the kinetics of inflammatory reactions from a local and systemic point of view.

Prostanoid release by macrophages at a distance from an inflammatory site.

During the development of an acute inflammatory reaction induced in the rat pleural cavity by dextran, calcium pyrophosphate, saline or phosphate buffered saline, macrophages present at a distant site (peritoneal cavity) display an increased capacity to release prostanoids: prostaglandins, prostacyclin and thromboxane. Enhanced levels of 6-keto-PGF1 alpha were observed both in peritoneal lavages (experiments in vivo) and in macrophage supernatants after 24-h culture (experiments in vitro). TXB2 levels were mainly increased in peritoneal lavages and PGE2 in culture supernatants. In vivo, levels of prostanoids in the peritoneal cavity reached a maximum 24 h after the induction of pleurisy whatever the injected substance. In vitro, amounts of arachidonic acid metabolites were highest in supernatants of cultured peritoneal macrophages harvested 72 h after the pleural injection of dextran or CaPP. These results show that the regulation of macrophage functions is closely related to prostanoid production, especially the release of PGE2 and PGI2.