Ambiguity of the influence of cytokines IL-8, IL-17A, TNFα, AND IFNγ on the antigen presenting CD66b⁺CD16⁺CD33⁺HLA-DR⁺ subpopulation of neutrophil granulocytes in children with acute hematogenic osteomyelitis

Abstract

Dysfunctions of the immune system, in turn, of neutrophil granulocytes (NG), are the cause of the emergence and progression of the focus of infection in bone tissue and bone marrow in acute hematogenous osteomyelitis (AHO). When colonizing bones, S. aureus, osteoblasts, osteocytes and macrophages secrete chemoattractants and cytokines, which initiate the influx of large amounts of NG into the site of infection, which, in turn, secrete cytokines and form an inflammatory microenvironment that promotes the formation of osteoclasts that resorb bone. It is known that NG activated by cytokines undergo functional and phenotypic changes. In this regard, detecting the cytokines that lead to the transformation of the NC phenotype into an antigen-presenting cell (APC) in AHO is of interest. Goal, to determine the levels of neutrophil-associated serum cytokines IL-8, IL-17A, TNFα, IFNγ and their relationship with numerous and phenotypic characteristics of subpopulations CD66b+CD16+CD33+HLA-DR-, CD66b+CD16+CD33+HLA-DR+NG in localized and septicopyemic forms of CSO in children.Children (N = 28) aged 8-15 years with AHO were studied: group 1 – 20 children with a localized form; group 2 – 8 children with septicopyemic form; and a comparison group of 13 conditionally healthy children. The number of NG subpopulations CD66b+CD16+CD33+HLA-DR+, CD66b+CD16+CD33+HLA-DR-, receptors mean expression intensity (MFI) (FC 500, mAb Beckman Coulter, USA); serum cytokines IL-8, IL-17A, TNFα, IFNγ ELISA (ASCENT, Finland), test systems Cloud-Clone Corp. (USA).The appearance of two activated subpopulations in the peripheral blood (PB) of children with various forms of AHO severity were found: CD66b+CD16+CD33+HLA-DR+ with the APC phenotype, capable of presenting the S. aureus superantigen for T lymphocytes and a subpopulation with high cytotoxic activity CD66b+CD16+CD33+HLA-DR- while concentrations of serum cytokines IFNγ, IL-17 are high and levels of TNFα are increased. Due to the fact that the NG activation range correlates with the range of inflammatory tissue damage, including bone tissue, determination of the level of IFNγ, IL-17 can be useful for assessing the severity of AHO, and also possibly for monitoring infectious and inflammatory processes occurring in the bone tissue.Taking into account the leading role of NG in various inflammatory reactions, determining the expression of HLA-DR, in order to identify the manifestation of the APC-NG subpopulation in peripheral blood, may have diagnostic value not only for AHO, but also for other manifestations of infectious and inflammatory diseases.

Keywords

• neutrophil granulocytes
• antigen-presenting subpopulation
• cytokines
• acute hematogenous osteomyelitis
• localized form
• septicopyemic form
• children