Aspects of monocyte function in cirrhosis

Abstract

Aspects of monocyte function have been studied in patients with cirrhosis. Monocyte spreading, chemotaxis, bacterial phagocytosis and killing, and production of lysosamal enzymes were found to be significantly reduced in cirrhotics compared to controls. Studies suggested that these defects were due to the presence of an inhibitory substance in cirrhotic serum which might have originated from the portal venous system. Significantly increased levels of immune complexes were demonstrated in portal serum compared to systemic serum and these, rather than the presence or absence of endotoxin, were shown to correlate with the amount of lysosanal enzymes produced when the samples were added to normal monocytes. Studies of immunoregulation in patients with chronic hepatitis were also undertaken. Suppressor T-cell actvity was shown to be reduced but results varied depending on which responder cells were used. On the contrary, significantly increased monocyte-mediated prostaglandin producing suppressor cell activity was demonstrated in these patients and in patients with other forms of cirrhosis. This appeared to be secondary to the cirrhosis and to account, at least in part, for the cellular hyporesponsiveness seen in patients with cirrhosis. There was no demonstrable relationship between the monocyte mediated and the T-lymphocyte suppressor cell activity, and no evidence of HLA linkage. Studies on the inhibitory action of cirrhotic serum on lymphocyte responses suggested that this was also monocyte mediated and prostaglandin dependent. Further in vitro studies showed that testosterone and progesterone affected T-cell suppression but not monocyte mediated suppression suggesting that some of the abnormalities in patients with cirrhosis might be due to the endocrine changes which are known to occur secondary to cirrhosis. Studies in patients with scleroderma and inflammatory bowel disease showed that increased prostaglandin producing suppressor cell activity was not specific to cirrhosis and might be a marker of abnormal fibrogenesis rather than of abnormal immunoregulation. The reduced T-cell suppressor activity in inflammatory bowel disease, which had previously been reported by others, could not be confined and there was no evidence that sulphasalazine, a drug of known benefit in these patients, affected the immunoregulatory system in any way or possessed antiprostaglandin properties. Finally studies of the humoral immune system showed that lymphocytes fran patients with cirrhosis produced more immunoglobulin than those fran controls and, using this assay to study cirrhotic hypergammaglobulinaemia, it is suggested that cirrhotic hypergammaglobulinaemia is mainly due to non-specific B cell stimulation rather than to defective suppressor cell function. This is also not a specific finding as patients with inflammatory bowel disease were also noted to have 4- reased spontaneous imnunoglobulin production. Furthermore in these patients a specific defect of IgA synthesis was found which may be of imnunopathogenic importance.

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