Ward P A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.
Ann N Y Acad Sci. 1996 Oct 31;796:104-12. doi: 10.1111/j.1749-6632.1996.tb32572.x.
The roles of complement, proinflammatory cytokines and regulatory cytokines in lung inflammatory injury are becoming defined. Like the proinflammatory cytokines (TNF alpha and IL-1), complement activation products (C5a and/or the membrane attack complex, C5b-9) can directly activate endothelial cells to cause upregulation of adhesion molecules (P-selectin) or can function in a synergistic manner with TNF alpha to cause enhanced upregulation of ICAM-1 and E-selectin. The beta chemokine, MIP-1 alpha, appears to function in vivo as an autocrine activator, enhancing TNF alpha production by pulmonary macrophages, which, in turn, enhances the inflammatory response. Finally, IL-4 and IL-10 have strong regulatory effects by suppressing in vivo production of TNF alpha. There is now compelling evidence to suggest that, in IgG immune-complex-induced lung inflammation in rats, endogenous IL-10 is produced and regulates the intensity of the inflammatory response. Blocking of endogenous IL-10 substantially increases lung TNF alpha production, the recruitment of neutrophils, and the intensity of lung inflammatory injury. Accordingly, the network of cytokines carefully regulates lung inflammatory responses.
