Specific binding of interleukin 1 (IL-1)β and IL-1 receptor antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor type I

doi:10.1016/1043-4666(93)90032-Z

Cytokine

Volume 5, Issue 5, September 1993, Pages 427-435

https://doi.org/10.1016/1043-4666(93)90032-Z Get rights and content

Abstract

Molecules that bind recombinant interleukin 1 (rIL-1)β and rIL-1 receptor antagonist (rIL-1ra) with high affinity were detected in sera of healthy individuals. rIL-1β bound with dissociation constants in the nanomolar range, and the serum binding capacity was 40–50 ng/ml. rIL-1ra bound with 30 times higher affinity, and the serum binding capacity was 0.7-1 ng/ml. Rabbit antibodies against the recombinant-derived extracellular part of human IL-1 receptor type 1 (rsIL-1RI) selectively inhibited the binding of ¹²⁵I-rIL-1ra to the serum factor(s). Almost 70% of the high-affinity IL-1ra-binding capacity was recovered after immunosorption with these antibodies. Binding of ¹²⁵I-rIL-1ra to rsIL-1RI was blocked by rIL-1α and by rIL-1β. In contrast, the purified rIL-1ra-binding factor (IL-1raBF) failed to bind rIL-1α and rIL-1β. Gel filtration chromatography indicated a 1:1 binding of rIL-1β and rIL-1ra to their respective serum factors. The apparent molecular size of both serum factors was 70–80 kDa. Using SDS-PAGE and autoradiography, IL-1raBF had a molecular size of 60 kDa. We conclude that IL-1raBF, a serum factor which selectively and with high affinity binds IL-1ra (Kd = 70 pM), is related to or identical with a soluble form of IL-1RI. If upregulated during disease, IL-1raBF may constitute yet another level of natural regulation of IL-1 bioactivities.

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Original contributionSpecific binding of interleukin 1 (IL-1)β and IL-1 receptor antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor type I

Abstract

Blood

Immunol Today

Clin Immunol Immunopathol

J Biol Chem

J Biol Chem

Cytokine

Blood

Cytokine

Cytokine

Cytokine

Immunol Today

Cell

Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist

J Clin Invest

Clinical significance of cytokines

IL-1α is produced by T lymphocytes activated via the CD2 plus CD28 pathways

J Immunol

Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta

Transition from interleukin 1β (IL-1β) to IL-1α production during maturation of inflammatory macrophages in vivo

J Exp Med

Production of a 26,000-Dalton interleukin 1 inhibitor by human monocytes is regulated by granulocyte-macrophage colony-stimulating factor

Cytokine

Original contribution
Specific binding of interleukin 1 (IL-1)β and IL-1 receptor antagonist (IL-1ra) to human serum. High-affinity binding of IL-1ra to soluble IL-1 receptor type I