25-hydroxyvitamin-d-2 and Tuberculosis--Pulmonary

To evaluate whether tuberculosis-associated hypercalcemia is related to abnormal synthesis of 1,25-dihydroxyvitamin D (1,25[OH]2D) and whether ketoconazole administration may be useful in treating tuberculosis-associated hypercalcemia.. Case study.. Endocrine Unit, Pediatric Clinic, University of Pisa (Italy).. Two boys (aged 10.5 years and 14.7 years) with active tuberculosis and hypercalcemia.. At admission, serum 1,25-dihydroxyvitamin D levels were elevated. Oral ketoconazole administration (3.0 mg/kg every 8 hours) decreased 1,25-dihydroxyvitamin D levels within the first week of therapy (from 208.8 to 57.6 pmol/L [-72.4%] in one boy and from 321.6 to 115.2 pmol/L [-64.2%] in the other). We also found a coincident normalization of serum ionized calcium concentration (from 1.45 to 1.24 mmol/L [-13.0%] in one boy and from 1.55 to 1.26 mmol/L [-17.0%] in the other).. Abnormal elevated levels of 1,25-dihydroxyvitamin D caused hypercalcemia in our patients; ketoconazole administration may be effective in the treatment of hypercalcemia in patients with tuberculosis, which decreases 1,25-dihydroxyvitamin D synthesis.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Calcitriol; Calcium; Child; Creatinine; Humans; Hydrocortisone; Hypercalcemia; Ketoconazole; Male; Parathyroid Hormone; Phosphorus; Radiography; Thyroid Function Tests; Tuberculosis, Pulmonary

Control of human tuberculosis (TB) requires induction and maintenance of both macrophage and T cell effector functions. We demonstrate that pulmonary TB patients with a vitamin D deficiency had significantly reduced local levels of the vitamin D-inducible antimicrobial peptide LL-37 in granulomatous lesions compared to distal parenchyma from the infected lung. Instead, TB lesions were abundant in CD3(+) T cells and FoxP3(+) regulatory T cells as well as IgG-secreting CD20(+) B cells, particularly in sputum-smear positive patients with cavitary TB. Mycobacteria-specific serum IgG titers were also elevated in patients with active TB. An up-regulation of the B cell stimulatory cytokine IL-21 correlated with mRNA expression of CD20, total IgG and also IL-10 in the TB lesions. Altogether, vitamin D-deficient TB patients expressed a weak antimicrobial response but an IL-21 associated expansion of IgG-secreting B cells combined with a rise in FoxP3(+) regulatory T cells at the local site of infection.

Topics: 25-Hydroxyvitamin D 2; Adult; Antigens, CD20; Antimicrobial Cationic Peptides; B-Lymphocytes; Calcifediol; Cathelicidins; Female; Forkhead Transcription Factors; Granuloma; Humans; Immunoglobulin G; Interleukin-10; Interleukins; Lung; Male; Middle Aged; Mycobacterium tuberculosis; T-Lymphocytes, Regulatory; Tuberculosis, Pulmonary; Vitamin D Deficiency