The following is a summary of “Excessive IL-10 and IL-18 trigger hemophagocytic lymphohistiocytosis–like hyperinflammation and enhanced myelopoiesis,” published in the November, 2022 issue of Allergy and clinical immunology by Tang, et al.


A potentially fatal disease called hyperinflammation was linked to several clinical illnesses defined by excessive immune activity and tissue damage. IL-10 may play a pathogenic function, although its contribution to the development of hyperinflammation was unknown despite recent rumors to the contrary. IL-18 and IL-10 may work together to induce the establishment of a hyper inflammatory state, according to clinical evidence from hemophagocytic lymphohistiocytosis (HLH), a classic hyperinflammatory condition. For a study, researchers sought to learn more about how IL-10 and IL-18 work together to cause inflammation.

First, a thorough plasma cytokine profile for 87 individuals with secondary HLH was shown and examined. Then, using a transgenic mouse model and cultured macrophages, they looked at the general and cellular consequences of coelevated IL-10 and IL-18. The clinical significance of IL-10/IL-18-mediated cellular signatures was investigated using single-cell RNA sequencing on the monocytes/macrophages recovered from secondary HLH patients. In HLH animal models, IL-10 blockade’s therapeutic effectiveness was examined.

Excessive levels of circulating IL-10 and IL-18 caused mice to develop a fatal hyperinflammatory illness that mirrored the HLH characteristics. The disease caused peripheral lymphopenia and a startling change toward increased myelopoiesis in the bone marrow. Myeloid cell-recruiting chemokines were strongly expressed in cultured macrophages that had been polarized by IL-10 and IL-18 into a unique proinflammatory state. When HLH was present, macrophages had increased granzyme production and proteasome activity, which demonstrated that the IL-10/IL-18-mediated cellular characteristics were clinically relevant. In HLH mice models, blocking IL-10 offered protection from the fatal illness.

Blocking IL-10 is protective in HLH models, and elevated IL-10 and IL-18 were sufficient to cause HLH-like hyperinflammatory syndrome.

Reference: jacionline.org/article/S0091-6749(22)00904-6/fulltext