title: 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.
abstract: Serum immunoreactive interleukin (IL-)1 alpha, IL-4, IL-6 and tumor necrosis factor (TNF) alpha were measured in 42 patients with primary hypogammaglobulinemia (25 common variable immunodeficiency (CVI), 10 congenital 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 percent 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 had detectable IL-4 or IL-6 levels. TNF alpha and IL-1 alpha were detected in only a few serum samples with no significant differences between patients and controls. In the CVI group elevated IL-6 levels were significantly associated to reduced numbers of CD4+ and CD19+ lymphocytes, elevated levels of neopterin and sCD8 antigen, and occurrence of splenomegaly and bronchiectasis. The raised IL-6 levels were confirmed in longitudinal testing, probably reflecting a characteristic immunological dysregulation in these patients. Cytokine alterations may play a role in the pathogenesis of the immunodeficiency and for the clinical 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 within the heterogeneous CVI group.
authors.affiliation: Medical Department A, University of Oslo, National Hospital, Rikshospitalet, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: S S
authors.initials: SS
authors.lastname: Frøland
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000151:congenital; D000368:Aged; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D016827:CD8 Antigens / Q000032:analysis; D002452:Cell Count; D017074:Common Variable Immunodeficiency / Q000097:blood*; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000097:blood* / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000166:cytology; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D012995:Solubility
chemical_list: D016827:CD8 Antigens; D015850:Interleukin-6; D015847:Interleukin-4; D001708:Biopterins; D019798:Neopterin