Abstract
Endotoxins, which cause septicemia and septic shock, stimulate macrophages and lymphocytes to elaborate tumor necrosis factor, and other lymphokines. These lympho-kines augment free radical generation by polymorphonuclear leukocytes, macrophages and other cells which may ultimately produce respiratory distress syndrome, multi-organ failure and irreversible shock seen in septicemia. Lymphokines and free radicals are also known to play a signifcant role in the pathogenesis of collagen vascular diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Thus, pneumonia represents an acute inflammatory condition from which recovery is usual, septicemia and septic shock are also due to bacterial infections but prognosis is poor and recovery is unusual, whereas collagen vascular diseases are characterized by chronic indolent inflammation. in order to delineate the role of free radicals and lymphokines, which are pro-inflammatory, and essential fatty acids which are anti-inflammatory, we studied their role in these conditions. An increase in free radical generation by human neutrophils in pneumonia, septicemia, RA and SLE was observed. Plasma phospholipid fatty acid analysis showed a decrease in the levels of gammalino-lenic acid (18:3, n-6, GLA). dihomoGLA (20:3, n-6. DGLA), arachidonic acid (AA. 20:4, n-6) and eicosapentaenoic acid (EPA, 20:5, n-3) in all three conditions, except that of GLA in pneumonia, and AA in RA and SLE. It was also observed that both n-3 and n-6 fatty acids can suppress human T-cell proliferation in vitro, and inhibit the secretion of both TNF and IL-2 by lymphocytes in vitro. The growth inhibitory effect and suppression of T-cell TNF and IL-2 secretion by n-3 and n-6 fatty acids was not blocked by cyclo-oxygenase and lipoxygenase inhibitors, suggesting that eicosanoids do not participate in these processes. These results indicate that free radicals, lipid peroxides and essential fatty acidr play a significant role in pneumonia, septicemia and collagen vascular diseases and that, at least in part, the anti-inflammatory actions of fatty acids can be attributed to their action on T-cell, TNF and IL-2 production.