IN-VITRO INHIBITORY ACTIVITY OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-2 OF HUMAN-IMMUNOGLOBULIN PREPARATIONS

Human immunoglobulin preparations have been used in a number of clinic al settings with good results, although in many of them the mechanism of action is not yet known. One possible mechanism is the modulation o f cytokine activity. This study investigated the presence of inhibitor y activity in intravenous immunoglobulin (IVIg) and F(ab')(2) fragment preparations to two cytokines, tumor necrosis factor-alpha (TNF-alpha ) and interleukin-2 (IL-2). Cytotoxic activity of human recombinant TN F-alpha or TNF-alpha secreted by peripheral blood mononuclear cells (P BMC) on L929 cells and the proliferative activity of the IL-2 on CTLL- 2 cells were examined. Human serum albumin (HSA) was used as control. F(ab')(2) inhibited, in a dose-dependent fashion, the TNF-alpha activi ty secreted by PBMC serial dilutions or, at the higher concentrations (25 and 10 mg/ml), recombinant TNF-alpha activity. In contrast, IVIg w as able to inhibit only at 25 and 10 mg/ml the TNF-alpha activity secr eted by any PBMC dilution tested, and did not inhibit the recombinant TNF-a activity. With IL-2, however, even HSA was able to inhibit its p roliferative activity, possibly through a carrier effect. The IVIg inh ibition of IL-2 activity was not different from that of HSA, but F(ab' )(2), at 12.5 mg/ml, was capable of inhibiting significantly more the IL-2 activity than HSA. Our results suggest an anticytokine effect of the immunoglobulin preparations that this activity may be mainly media ted by variable regions of the immunoglobulins, and that the more pron ounced effect of F(ab')(2) may be due to its greater molar concentrati on compared to intact IgG molecules.