title: Binding of cytokines to pharmaceutically prepared human immunoglobulin.
abstract: Pharmaceutically prepared IgG, pooled from sera of over 2,000 normal individuals, contained both monomeric and dimeric IgG. Each type of IgG bound 125I-labeled interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. Increased binding to IgG was observed if 125I-IL-1 beta was denatured by heating to 39 degrees C. However, the binding of both nondenatured and denatured 125I-IL-1 beta was not inhibited by unlabeled IL-1 beta. In contrast, binding of 125I-IL-1 alpha, 125I-IL-6, and 125I-TNF alpha was inhibited by the corresponding unlabeled cytokine. Papain-digestion of IgG abolished binding of 125I-TNF alpha but failed to influence the displaceable binding of 125I-IL-1 alpha and 125I-IL-6. 125I-TNF alpha was a mixture of trimeric and monomeric forms, the latter being the predominant form at lower concentrations. The apparent saturability of 125I-TNF alpha was explained by a higher nonspecific binding of monomeric than of trimeric 125I-TNF alpha to IgG. The amounts of cytokine antibodies in IgG preparations would contribute approximately 2 micrograms anti-IL-1 alpha IgG and 1 microgram anti-IL-6 IgG per kg body wt during high dose immune globulin therapy. In conclusion, pharmaceutical preparations of human IgG contain specific and neutralizing, high affinity antibodies against IL-1 alpha and IL-6, but not against TNF alpha or IL-1 beta. There are significant methodological pitfalls that hamper detection of IgG autoantibodies against cytokines.
authors.affiliation: Laboratory of Medical Immunology, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Svenson
authors.forename: M B
authors.initials: MB
authors.lastname: Hansen
authors.forename: K
authors.initials: K
authors.lastname: Bendtzen
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood*; D001688:Biological Products / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003902:Detergents / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008892:Milk; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000906:Antibodies; D001688:Biological Products; D016207:Cytokines; D003902:Detergents; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha