Clinical and immunological efficacy of immunotherapeutic program after surgical treatment of children with various forms of acute peritonitis

Abstract

Acute peritonitis (AP) is among the most frequent and severe conditions in pediatric abdominal surgery. Due to development of antibiotic resistance and increasing number of atypical infectious and inflammatory diseases (IIDs), a lot of specialists suggest combined treatments for these patients which should include not only surgical and etiotropic approaches, as well as therapy aimed at correction of functional defects of immunity. Neutrophilic granulocytes (NGs) reepresent a unique population of cells of primary anti-infectious immune response. Functional NG defects in pediatric AP play a leading role in development, prevalence, severity of peritoneal inflammation, and response to the therapy. Special role is given to functionally significant NG subsets responsible for triggering and implementation of phagocytosis and microbicidal properties of NG in purulent lesions and inflammatory process in children. There is an urgent need for development of new approaches to targeted immunomodulatory therapy in order to correct the NG dysfunction. The aim of the present study was to arrange the programs of immunomodulatory therapy after surgical treatment of immunocompromised children with various forms of acute peritonitis followed by subsequent evaluation of its clinical and immunological efficacy. The study included 12 immunocompromised children aged 5-12 years with different clinical course of acute peritonitis. The study group 1 included patients with local nonrestricted AP; study group 2 involved children with diffuse AP. The comparison groups consisted of 6 children who received standard therapy, i.e., clinical comparison groups 1 and 2, matched for sex, age and diagnosis. A control group consisted of 18 conditionally healthy children at similar age. Clinical examination included collection of the patient’s history, complaints, objective examination and clinical course assessment of the underlying disease. Immunological study included determination of receptor, phagocytic and microbicidal activity of NCs; assessment of NC subpopulations by their numbers and phenotype using flow cytometry, i.e., the cells co-expressing CD64, CD16, CD32, CD11b, with testing density of these membrane receptors by the MFI approach. Targeted immunomodulatory therapy programs were applied for treatment of children with unrestricted local and diffuse AP, taking into account clinical features of AP, as well as changes in number and phenotype of NC subpopulations, and impairment of their effector function. The standards of postsurgical treatment in the children with various forms of AP included different courses of treatment with Imunofan (Hexapeptide – arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine; HP) using different schedules and duration. We have shown high clinical and immunological efficiency of these therapeutic programs. Thus, reversal of adequate NG functioning was observed, including positive rearrangements of negatively transformed functional NG subpopulations. In this respect, a positive clinical effect was noted in children with atypical AP with various clinical courses, i.e., absence of postsurgical complications, rapid regression of intoxication signs, normalization of body temperature, reduced volume of antibiotic therapy and shorter hospitalization terms.

Keywords

• neutrophilic granulocytes
• dysfunction
• acute peritonitis
• hexapeptide
• immunomodulatory therapy
• children