Pathogenetic rationale for usage of recombinant interleukins in the patients with mandibular fractures to prevent post-traumatic osteomyelitis

Abstract

The paper presents the results on spontaneous and induced production of IFNγ, IL-4, IL-13 cytokines in blood cells of patients with mandibular fractures and post-traumatic osteomyelitis. Osteomyelitis of the jaw represents one of the urgent challenges in modern medicine. There are many reasons for development of purulent necrotic processes of the jaw bones, including disorders of innate and adaptive immune response. Currently, the immunological aspects of post-traumatic complications of maxillofacial region remain poorly understood. There are no unambiguous and systematic studies of immune mechanisms in pathogenesis of post-traumatic osteomyelitis of the lower jaw. The aim of our study was to theoretically confirm application of recombinant interleukins (IL-1β, IL-2, IFNγ) in the patients with jaw fractures, in order to prevent osteomyelitis, as based on the studies of spontaneous and induced cytokine production (IFNγ, IL-4, IL-13). Spontaneous and stimulated production of IFNγ, IL-4, and IL-13 cytokines by blood cells was determined using specific reagent kits from RD Diagnostic Inc. (USA). The results were recorded using an ELISA Multiscan analyzer (Finland). Statistical significance of intergroup differences was determined by the Mann–Whitney method. The level of statistical significance at which the null hypotheses were rejected was 0.05. To stratify the cases of post-traumatic osteomyelitis and uncomplicated mandibular fracture, the models were developed with a singlelayer neural network, using the nnet R-studio package. To assess quality of the models, the areas under the ROC curves (AUC), Akaike criterion (AIC), and the relative classification accuracy (OTC) were used, which was determined as the ratio of correctly established model diagnosis numbers to the total number of patients. The study results demonstrate that the patients with mandibular fractures exhibit a moderate impairment of LPS-induced IL-4 and IFNγ production by leukocytes with IL-13 activation. In presence of osteomyelitis, this imbalance is promoted, thus suggesting an impaired ability of the cells to produce IL-4 and IFNγ. An opportunity for usage immunomodulation when treating the patients with mandibular fractures is represented by P = 1/(1+e-z) where z is defined via IL-1β, IL-2 and IFNγ levels on the first day of observation. In vitro supplementation with recombinant IL-1β and IFNγ modulates cell function, improving the cytokine profile. The prognostic models, imitating binary logistic regression, were used to demonstrate that recombinant IL-1β could be used to prevent patients with mandibular fractures from developing post-traumatic osteomyelitis (AIC = 13.2, AUC = 0.96, р = 0.026).