Significance of interleukins and chemokines in development of vincristine polyneuropathy in children with acute lymphoblastic leukemia

Abstract

Objective. To analyze the content of interleukins, chemokines in plasma and liquor of children with acute lymphoblastic leukemia depending on the development of vincristine polyneuropathy.

Materials and methods. A single-center prospective cohort non-randomized study was conducted involving 131 children aged 3 to 17 years with acute lymphoblastic leukemia who received chemotherapy according to the protocol. The content of interleukins and chemokines in blood plasma and liquor was assessed with the subsequent comparative analysis of the indicators in two groups depending on the development of vincristine polyneuropathy. The level of the studied parameters was determined before the administration of chemotherapy and on the 36th day of treatment using multiparametric immunofluorescence analysis.

Results. In the studied cohort of patients vincristine polyneuropathy was registered in 80.9 % (n = 106) of patients. In the majority of cases – 84.9 % (n = 90) neurotoxic complication developed during the induction stage of chemotherapy. In the clinical picture there dominated sensory and motor disorders in 70.7 % (n = 75) of patients. The data of electrophysiologic study testified to motor axonal polyneuropathy with peroneal nerves lesion. When comparing the primary level of interleukins with their concentration after completion of the induction stage of chemotherapy, it was found that in children without vincristine polyneuropathy there was a statistically significant increase in almost all proinflammatory and anti-inflammatory interleukins. Besides, in this group high and medium direct statistically significant correlations between these cytokines were established. Especially close correlations were noted between pro-inflammatory IL-1, IL-17 and anti-inflammatory interleukins (IL-10, IL-13, IL-22 and IL-27). Additionally, in patients with vincristine polyneuropathy, a 3.7-fold increase in CXCL10 (IP-10) and a 1.4-fold increase in CXCL12 (SDF-1α) chemokines (p = 0.005 and p = 0.054, respectively) was detected in the liquor during the completion of the induction phase of chemotherapy.

Conclusions. The balanced interleukin response in children with acute lymphoblastic leukemia receiving vincristine probably reflects a link between the immune and nervous systems aimed at preventing peripheral nerve damage. An imbalance of proinflammatory and anti-inflammatory interleukins may contribute to the development of vincristine polyneuropathy. Significant increase in the content of chemokines CXCL10 (IP-10) and CXCL12 (SDF-1α) in the liquor of children with vincristine polyneuropathy gives grounds to consider them as biological markers of vincristine neurotoxicity.

Keywords

polyneuropathy / acute leukemia / vincristine / interleukins / chemokines

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