LYMPHOTOXIN-ALPHA (TNF-BETA) DURING SEPSIS

T cell release of lymphotoxin-alpha (LT-alpha, or TNF-beta) is stimula ted by pyrogenic exotoxins of Gram-positive bacteria and mitogens, In contrast to TNF-alpha, it is unknown whether LT-alpha plays any role i n the pathogenesis of sepsis and, in particular, the pathogenesis of G ram-positive sepsis, Sera from patients with sepsis were examined for LT-alpha and compared with normal volunteers and pregnant women, LT-al pha was detected in 33% of sepsis sera (mean 608.4 pg/ml SE 306), 16% of normal sera (mean 167 pg/ml SE 87) and 23% of sera from pregnant wo men (mean 714 pg/ml SE 191). These differences were not significant an d there were no differences within sepsis sera when grouped by the typ e of causative organism, or disease severity, LT-alpha detected by imm unoassay in serum was not bioactive, in contrast to that produced in c ell culture, Recombinant soluble TNF receptors (rSTNFR) neutralized th e bioactivity of recombinant LT-alpha at rSTNFR concentrations which d id not interfere with immunoreactivity and which are known to prevail in vivo. Hence, LT-alpha is unlikely to have a critical role in the pa thogenesis of sepsis, Much of the potential bioactivity of this lympho kine may be abrogated by TNFR in serum.