THE ACUTE-PHASE PROTEIN RESPONSE IN PATIENTS RECEIVING SUBCUTANEOUS IL-6

IL-6, tumour necrosis factor-alpha (TNF-alpha) and IL-1 are thought to be the key mediators of the acute phase response although much of the evidence is based an in vitro studies. It is not clear to what extent each of the acute phase proteins are regulated in vivo by each of the se cytokines. The aim of this study was to examine the effects of IL-6 treatment in eight patients with cancer on the concentrations of an e xtensive range of positive and negative acute phase proteins. It was p art of a larger investigation to assess the value of IL-6 in the manag ement of chemotherapy-induced thrombocytopenia. IL-6 was administered by a daily subcutaneous injection for 7 days at a dose level of 1, 3, or 10 mu g/kg/day. Increases in the positive acute phase proteins, ser um amyloid A, C-reactive protein, alpha(1)-acid glycoprotein, alpha(1) -antichymotrypsin, haptoglobin, alpha(1)-antitrypsin, fibrinogen, comp lement component C3, and caeruloplasmin, were observed, with the great est incremental changes and fastest responses being seen for C-reactiv e protein and serum amyloid A protein. The negative acute phase protei ns transferrin, transthyretin and retinol binding protein all fell to a nadir within 48-96 h after the first IL-6 injection. Increases in co mplement component C4 were only found in two patients, which may be re lated to the increase in circulating TNF-alpha concentrations found on ly in these patients. This study has therefore shown that IL-6 is capa ble of causing changes in the majority of acute phase proteins in vivo . Although secondary induction of TNF-alpha was not observed in the ma jority of patients examined, it is still possible however that other c ytokines involved in regulation of the acute phase response, such as I L-1, may have been induced and contributed to the overall response.