Cytokine Profile Associated with Selective Removal of Natural Anti-[alpha]Gal Antibodies in a Sepsis Model in Gal-KO Mice

Selective depletion of natural anti-Gal[alpha]1-3Gal[beta]1-4GlcNAc (so-called anti-[alpha]Gal) antibodies is achieved in [alpha]1,3-galactosyltransferase knockout (Gal-KO) mice by administration of the soluble glycoconjugate of [alpha]Gal GAS914. This molecule removed up to 90% of natural circulating anti-[alpha]Gal antibodies without causing unspecific production of cytokines in wild-type (CBA) and Gal-KO mice. However, the removal of anti-[alpha]Gal antibodies in Gal-KO mice with GAS914 in the context of sepsis after cecal ligation and puncture (CLP) was associated with a significant increase in the production of leptin, CXLC1, CXLC13, and TIMP-1 cytokines compared to vehicle (PBS)-treated controls. Despite the current lack of understanding of the underlying mechanism, our data suggest a putative role of natural anti-[alpha]Gal antibodies in the regulation of some cytokines during sepsis.