ELEVATED SERUM LEVELS OF INTERLEUKIN-4 AND INTERLEUKIN-6 IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY (CVI) ARE ASSOCIATED WITH CHRONIC IMMUNE ACTIVATION AND LOW NUMBERS OF CD4(+) LYMPHOCYTES

Serum immunoreactive interleukin (IL-)1 alpha, IL-4, IL-6 and tumor ne crosis factor (TNF) alpha were measured in 42 patients with primary hy pogammaglobulinemia (25 common variable immunodeficiency (CVI), 10 con genital hypogammaglobulinemia (CH), 7 X-linked agammaglobulinemia (XLA ), and in 21 healthy controls. The cytokine levels were correlated to other immunological parameters including serum levels of neopterin and soluble CD8 (sCD8) antigen. IL-6 was detectable in 48% and IL-4 in 36 % of the CVI patients, but in none of the controls. Seventy-five perce nt of the CVI patients with elevated IL-4 levels had detectable IL-6. In contrast, no patients in the XLA group and only three CH patients h ad detectable IL-4 or IL-6 levels. TNF alpha. and IL-1 alpha were dete cted in only a few serum samples with no significant differences betwe en patients and controls. In the CVI group elevated IL-6 levels were s ignificantly associated to reduced numbers of CD4(+) and CD19(+) lymph ocytes, elevated levels of neopterin and sCD8 antigen, and occurrence of splenomegaly and bronchiectasis. The raised IL-6 levels were confir med in longitudinal testing, probably reflecting a characteristic immu nological dysregulation in these patients. Cytokine alterations may pl ay a role in the pathogenesis of the immunodeficiency and for the clin ical manifestations in CVI patients. Alternatively, elevated cytokine levels may be only a marker of chronic immune activation, particularly in monocytes, possibly delineating a distinct subgroup of patients wi thin the heterogeneous CVI group. (C) 1994 Academic Press, Inc.