Cathelicidin Antimicrobial Peptide (CAMP) and Its Correlation with Serum 25 Hydroxy Vitamin D in Under-Five Children with Pneumonia

Abstract

Cathelicidins are human peptides involved in innate immunity, and are believed to be mediators of vitamin D-related immune benefits. We aimed to evaluate the correlation between serum levels of 25 hydroxy vitamin D (25(OH)D) and serum cathelicidin antimicrobial peptide (CAMP) in children hospitalized with severe pneumonia. This was a secondary analysis from a larger randomized double-blind placebo-controlled trial on vitamin D supplementation in severe pneumonia. Children aged 6 months to 5 years with the World Health Organization (WHO) defined severe pneumonia were included. Any child with rickets, immunodeficiency, or chronic illness was excluded. Baseline serum CAMP, serum 25(OH)D, and immunoglobulins were measured and analyzed. A total of 163 under-five children were recruited with mean (standard deviation) age 16.4 (13.0) months. The median (interquartile range [IQR]) serum CAMP was 12.5(8.0–20.0) ng/mL and serum 25(OH)D was 14.4 (8.4–24.2) ng/mL. There was no significant correlation between serum cathelicidin and serum 25(OH)D (r = −0.064, p = 0.415). Serum 25(OH)D was low (<20 ng/mL) in 105(64.4%) participants. Median (IQR) serum CAMP was comparable between children with low (<20 ng/mL) and normal serum 25(OH)D levels (13.0 [8.2, 22.1] and 12.0 [8.0, 17.4] pg/mL; p = 0.2). Serum cathelicidin showed significant positive correlation with serum immunoglobulin M levels (r= 0.456, p < 0.001). There was no significant correlation between serum cathelicidin and serum vitamin D in under-five children hospitalized with severe pneumonia.

Keywords

cathelicidin - vitamin D - infection - children - pediatric

Any Previous Presentation of the Manuscript

We declare that manuscript has not been previously published nor is not being considered for publication elsewhere.

Authors' Contribution

PG, DS, PD, and AKB contributed to study design and conceptualization. AD and NK were involved in data acquisition and analysis. Initial draft was written by AD and NK. The manuscript was revised with critical inputs from DS, PD, AKB, and PG. All authors have read and approve the final content of the manuscript.

Publikationsverlauf

Artikel online veröffentlicht:
13. Juli 2023

• References

• 1 Agier J, Efenberger M, Brzezińska-Błaszczyk E. Cathelicidin impact on inflammatory cells. Cent Eur J Immunol 2015; 40 (02) 225-235
• 2 Tjabringa GS, Rabe KF, Hiemstra PS. The human cathelicidin LL-37: a multifunctional peptide involved in infection and inflammation in the lung. Pulm Pharmacol Ther 2005; 18 (05) 321-327
• 3 Vasilyevna Belyaeva I, Pavlovitch Churilov L, Robertovnа Mikhailova L, Vladimirovitch Nikolaev A, Andreevna Starshinova A, Kazimirovitch Yablonsky P. Vitamin D, cathelicidin, prolactin, autoantibodies, and cytokines in different forms of pulmonary tuberculosis versus sarcoidosis. Isr Med Assoc J 2017; 19 (08) 499-505
• 4 Arikoglu T, Kuyucu S, Karaismailoglu E, Batmaz SB, Balci S. The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children. Allergy Asthma Proc 2015; 36 (04) 51-58
• 5 Majewski K, Kozłowska E, Żelechowska P, Brzezińska-Błaszczyk E. Serum concentrations of antimicrobial peptide cathelicidin LL-37 in patients with bacterial lung infections. Cent Eur J Immunol 2018; 43 (04) 453-457
• 6 García-Quiroz J, García-Becerra R, Santos-Martínez N, Avila E, Larrea F, Díaz L. Calcitriol stimulates gene expression of cathelicidin antimicrobial peptide in breast cancer cells with different phenotype. J Biomed Sci 2016; 23 (01) 78
• 7 Lei GS, Zhang C, Cheng BH, Lee CH. Mechanisms of action of vitamin D as supplemental therapy for pneumocystis pneumonia. Antimicrob Agents Chemother 2017; 61 (10) e01226-e17
• 8 Quraishi SA, De Pascale G, Needleman JS. et al. Effect of cholecalciferol supplementation on vitamin D status and cathelicidin levels in sepsis: a randomized, placebo-controlled trial. Crit Care Med 2015; 43 (09) 1928-1937
• 9 Gupta P, Dewan P, Shah D. et al. Vitamin D supplementation for treatment and prevention of pneumonia in under-five children: a randomized double-blind placebo controlled trial. Indian Pediatr 2016; 53 (11) 967-976
• 10 World Health Organization. Pocket Book of Hospital care for children: guidelines for the management of common illnesses with limited resources. Geneva: World Health Organization; 2005. Accessed April 26, 2023 at: http://www.who.int/maternal_child_adolescent/documents/9241546700/en/
• 11 Gupta P, Dabas A, Seth A. et al. Indian Academy of Pediatrics Revised (2021) guidelines on prevention and treatment of vitamin D deficiency and rickets. Indian Pediatr 2022; 59 (02) 142-158
• 12 Pinheiro da Silva F, Machado MC. The dual role of cathelicidins in systemic inflammation. Immunol Lett 2017; 182: 57-60
• 13 Dixon BM, Barker T, McKinnon T. et al. Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults. BMC Res Notes 2012; 5: 575
• 14 Bhan I, Camargo Jr CA, Wenger J. et al. Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults. J Allergy Clin Immunol 2011; 127 (05) 1302-4.e1
• 15 Lambert AA, Kirk GD, Astemborski J. et al. A cross sectional analysis of the role of the antimicrobial peptide cathelicidin in lung function impairment within the ALIVE cohort. PLoS One 2014; 9 (04) e95099
• 16 Gad GI, Abushady NM, Fathi MS, Elsaadany W. Diagnostic value of anti-microbial peptide, cathelicidin in congenital pneumonia. J Matern Fetal Neonatal Med 2015; 28 (18) 2197-2200
• 17 Peng MY, Liu WC, Zheng JQ. et al. Immunological aspects of SARS-CoV-2 infection and the putative beneficial role of vitamin-D. Int J Mol Sci 2021; 22 (10) 5251
• 18 Gönen MS, Alaylıoğlu M, Durcan E. et al. Rapid and effective vitamin D supplementation may present better clinical outcomes in COVID-19 (SARS-CoV-2) patients by altering serum INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. Nutrients 2021; 13 (11) 4047
• 19 McNally JD, Nama N, O'Hearn K. et al. Vitamin D deficiency in critically ill children: a systematic review and meta-analysis. Crit Care 2017; 21 (01) 287