Circulating granulocyte-macrophage colony-stimulating factor and serum fatty acid composition in men and women

Atherosclerosis is increasingly recognized as an inflammatory disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a proinflammatory cytokine, recently implicated as a prominent component of the regulatory network involved in atherogenesis. We aimed to study the relationship between circulating GM-CSF levels and serum fatty acid (FA) composition in 78 healthy subjects. The latter was analyzed by gas-liquid chromatography and GM-CSF by a high-sensitivity commercial enzyme-linked immunosorbent assay (ELISA). Among women (n = 40), serum GM-CSF levels were found to be positively associated with the proportion of palmitic acid (C16:0) and negatively with linoleic acid (C18:2[omega ]-6), docosahexaenoic acid (DHA, C22:6[omega ]-3), and the proportion of total essential FA. After excluding smoking women (n = 6), the associations among GM-CSF and serum linoleic acid concentration (r= [minus ]0.49, P= .003), arachidonic acid (r= [minus ]0.52, P= .001), and DHA (r= [minus ]0.34, P= .04) were strengthened. The ratio of palmitic to linoleic and DHA acids was the single best predictor of serum GM-CSF in all subjects. Together with arachidonic acid, it contributed to 22% of the GM-CSF variance in women, after taking into account the effects of age, body mass index (BMI), blood pressure, and smoking status. None of these associations were observed among men. In conclusion, serum FA composition is associated with circulating GM-CSF specifically in women. As human arterial and venous smooth muscle cells release GM-CSF, and treatment of endothelial cells with oxidized low-density lipoproteins results in a rapid expression of GM-CSF, the mechanisms involved in these associations and the sex-linked differences should be further explored.