THE INFLUENCE OF MEMBRANE FLUIDITY, TNF RECEPTOR-BINDING, CAMP PRODUCTION AND GTPASE ACTIVITY ON MACROPHAGE CYTOKINE PRODUCTION IN RATS FEDA VARIETY OF FAT DIETS

The effects of different dietary fats on peritoneal macrophage plasma membrane fluidity, intracellular cyclic AMP (cAMP) production, GTP hyd rolysis and TNF binding and TNF-induced IL1 and IL6 production was inv estigated. After a four week period, fluidity, as determined by both f luorescence recovery after photobleaching (FRAP) and anisotropy was lo west and highest in animals fed corn and fish oil respectively. After eight weeks feeding, lateral membrane movements were decreased substan tially in fish, olive and coconut oil fed dietary groups, whereas an i ncrease in the corn oil fed group was observed, no effect was observed in macrophages from the butter fed group. However, an increase in the packing was observed in macrophages from all dietary groups except in the olive oil fed group. GTPase values for the coconut oil and butter groups were higher than in any other dietary group. After receiving t he diet for 8 weeks these differences between the groups were no longe r apparent. Exposure of macrophages to TNF had no effect on the rate o f GTP hydrolysis. A major enhancement of cAMP production became appare nt between weeks 4 and 8 of dietary treatment. After 4 weeks on the di et, values were significantly higher from cells of animals fed corn an d olive oils than from animals fed fish oil. After 8 weeks, while ther e was a general enhancement of production, further differences became apparent. Feeding corn and coconut oils resulted in the highest values and olive oil and chow in the lowest. It is proposed that fats rich i n n-3 fatty acids (fish oils) alter membrane fluidity, decrease TNF bi nding affinity, GTPase activity and cAMP production which appears not to modify cytokine production after short term dietary supplementation . However, after long term feeding it appears that increases in the se nsitivity of the TNF receptors plays a major role in modifying cytokin e production.