Azithromycin Reduces Markers of Vascular Damage in Pediatric Patients With Sickle Cell Disease

Peter N Uchakin; Vishwas S Sakhalkar; Francis C Dane; Olga N Uchakina; Jatayah N Sheed; William T Uphouse; Om V Sakhalkar

doi:10.14740/jh827

Azithromycin Reduces Markers of Vascular Damage in Pediatric Patients With Sickle Cell Disease

J Hematol. 2021 Aug;10(4):178-186. doi: 10.14740/jh827. Epub 2021 Jul 28.

Authors

Peter N Uchakin^{1

2}, Vishwas S Sakhalkar³, Francis C Dane⁴, Olga N Uchakina¹, Jatayah N Sheed⁵, William T Uphouse⁵, Om V Sakhalkar⁶

Affiliations

¹ Department of Biomedical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA.
² Department of Internal Medicine, Mercer University School of Medicine, Macon, GA 31207, USA.
³ Division of Pediatric Hematology/Oncology, Mercer University School of Medicine, Beverly Knight Olson Children's Hospital and HOPE Clinic at Atrium Health-Navicent, Macon, GA 31201, USA.
⁴ Department of Psychology, Radford University, Roanoke, VA 24013, USA.
⁵ Mercer University School of Medicine, Macon, GA31207, USA.
⁶ Augusta University, Augusta, GA, USA.

PMID: 34527114
PMCID: PMC8425801
DOI: 10.14740/jh827

Abstract

Background: Immunomodulatory effects of macrolides in chronic inflammation are well known. In this study, we tested our hypothesis that azithromycin (AZT) can decrease inflammation in pediatric patients with sickle cell disease (SCD).

Methods: The use of AZT as an anti-inflammatory agent was evaluated in double-blind, placebo-controlled, cross-over study for 8 weeks of treatment with 8 weeks of washout. Blood samples were collected before (PRE) and after (POST) each 8-week treatment period. Repeated measures analysis of variance (ANOVA) with post hoc multiple comparison procedures and Chi-square test were used for statistical analysis of the data. Complete blood count, distribution of the lymphocyte subsets, and plasma levels of markers of vascular damage were analyzed.

Results: A significant decrease in the number of leucocytes and granulocytes was observed in AZT group following treatment. An opposite dynamic was observed in placebo group; numbers of granulocytes significantly increased at POST interval. All markers of vascular damage were reduced in AZT group at POST interval with overall significance (P = 0.026). The most prominent significant changes were observed in levels of myeloid-related protein 8/14 (MRP8/14), lipocalin A (NGAL), matrix metalloproteinases (MMP) 9, and insulin-like growth factor-binding protein (IGFBP) 4. Plasma level of C-reactive protein (CRP) was significantly decreased in AZT group as well.

Conclusions: Data suggested that AZT may be beneficial in management of microvascular injury in SCD.

Keywords: Antibiotic; Inflammation; Macrolide; Vascular damage.