Immunoxel is affordable, safe, effective, fast-acting, commercially available immunotherapeutic intervention to supplement conventional TB chemotherapy. Clinicaltrials.gov ID: NCT01061593.

Introduction: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. Material and methods: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Results: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Conclusions: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines’ production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

ObjectiveImmunotherapy of tuberculosis (TB) to shorten treatment duration represents an unmet medical need. Orally delivered, tableted TB vaccine (V7) containing heat-killed Mycobacterium vaccae (NCTC 11659) has been demonstrated in prior clinical studies to be safe and fast-acting immune adjunct.MethodsThe outcome of Phase III trial of V7 containing 10 µg of hydrolyzed M. vaccae was evaluated in 152 patients randomized at 2:1 ratio: V7 (N = 100), placebo (N = 52). Both arms received conventional 1st or 2nd line TB drugs co-administered with daily pill of V7 or placebo.ResultsAfter one month mycobacterial clearance was observed in 68% (P < 0.0001) and 23.1% (P = 0.04) of patients on V7 and placebo. Stratified conversion rates in V7 recipients with drug-sensitive and multidrug-resistant TB were 86.7% and 55.6% vs 27.2% and 15% in placebo. Patients on V7 gained on average 2.4 kg (P < 0.0001) vs 0.3 kg (P = 0.18) in placebo. Improvements in hemoglobin levels, erythrocyte sedimentation rate and leukocyte counts were significantly better than in controls. Liver function tests revealed that V7 can prevent chemotherapy-induced hepatic damage.ConclusionOral M. vaccae is safe, can overcome TB-associated weight loss and inflammation, reduce hepatotoxicity of TB drugs, improve sputum conversion three-fold OR 3.15; 95%CI (2.3,4.6), and cut treatment length by at least six-fold. Longer follow-up studies might be needed to further substantiate our findings (Clinicaltrials.gov: NCT01977768).

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Wstęp: Gruźlica wielolekooporna (MDR-TB) stanowi poważny problem zdrowotny w pewnych regionach świata. Interleukiny 2 (IL-2), 4 (IL-4) i 10 (IL-10) odgrywają istotną rolę w immunopatogenezie gruźlicy. Podatność na gruźlicę wielolekooporną może być genetycznie uwarunkowana. Celem badania była ocena związku pomiędzy polimorfizmem genów IL-2, IL-4, IL-10 a występowaniem gruźlicy wielolekoopornej w populacji ukraińskiej. Materiał i metody: Do badania włączono 140 chorych na gruźlicę naciekową i 30 osób zdrowych (grupa kontrolna). Wyodrębniono grupę chorych na gruźlicę wielolekooporną (MDR TB) i gruźlicę z zachowaną opornością na leki przeciwgruźlicze (non-MDR TB). Zbadano polimorfizm T330G genu IL-2, C589T genu IL-4 i G1082A genu IL-10 przy zastosowaniu łańcuchowej reakcji polimerazy. Stężenia IL-2, IL-4 and IL-10 w surowicy oznaczono za pomocą testu ELISA. Wyniki: Przed leczeniem u chorych na gruźlicę stężenia w surowicy IL-2 były wyższe, a IL-4 i IL-10 niższe w porównaniu z grupą kontrolną. Stężenia IL-4 i IL-10 były istotnie niższe, podczas gdy stężenie IL-2 było istotnie wyższe w grupie MDR TB w porównaniu z pozostałymi chorymi (non- MDR TB). Opisane zmiany związane były z homozygotycznymi lub heterozygotycznymi mutacjami polimorficznymi C589T genu IL-4, G1082A genu IL-10 i T330G genu IL-2. Wnioski: Mutacje genów badanych cytokin mogą stanowić czynnik ryzyka gruźlicy i prowadzić do progresji i przewlekania się choroby. W grupie MDR TB genotypy heterozygotyczne badanych cytokin występowały najczęściej.