Mice C3HeB/FeJ infected with M. tuberculosis Erdman

T863

Triglycerides synthesis inhibitor

It increases 5-LOX products and decreases the production of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-β), prostanoids, bacillary load and neutrophil infiltration

43

Mice C57BL/6J infected with M. tuberculosis H37Rv

SC-26196

Inhibits FADS-2, ω-3 formation

Chronic infection induces the synthesis of new PUFA to generate eicosanoids (mainly AA). Inhibiting PUFA synthesis has no effect on bacterial growth in the liver or lung

44

Mice BALB/c infected with M. tuberculosis H37Rv

SBG or SBG + NA + conventional treatment

SBG is TGF-β inhibitor, NA is COX-2 inhibitor

Increased pneumonia in mice with blockers (SBG or NA), but less pulmonary fibrosis. Blocking agents enhance the activity of antibiotics

45

Mice BALB/c infected with M. tuberculosis H37Rv

NA

COX-2 inhibitor

Blocking COX-2 at the onset of infection causes increased interstitial and perivascular inflammation, pneumonic areas, and bacterial load. Advanced phase blockade of infection causes increased area of granuloma, IFN-γ, TNF-α, and iNOS with decreased pneumonic area and bacterial load

46

Mice C3HeB/FeJ infected with M. tuberculosis H37Rv

Ibuprofen + conventional treatment

Ibuprofeno is COX-2 inhibitor

Ibuprofen reduces the production of pro-inflammatory cytokines (IFN-γ, IL-1β, IL-6, IL-1α)

74

Swiss albino mice infected with M. tuberculosis H37Rv

Diclofenac + STR (streptomycin)

Diclofenac is COX-2 inhibitor

Diclofenac decreases inflammatory cytokines (IL-2, TNF-α, IFN-γ), induces antimicrobial activity, enhances antibiotic activity of STR and increases survival

47

Mice C3HeB/FeJ and CB6F1 infected with M. tuberculosis H37Rv and Erdman

Celecoxib or ibuprofen

Both are COX-2 inhibitors

Celecoxib impairs the immune response of CD4+ T cells. The effect of both COX-2 inhibitors depends on the initial bacterial load of the infection, when the bacterial load and inflammation are very high, a benefit is seen when using COX-2 inhibitors

75

Mice C3HeB/FeJ infected with M. tuberculosis H37Rv

Aspirin

+ rifafour

Aspirin is COX-2 inhibitor

Aspirin reduces IL-1α, increases TNF-α, IL-17, IL-1β and IL-6 and reduces pulmonary damage

42

Mice BALB/C infected with M. tuberculosis H37Rv

Aspirin or ibuprofen + INH

Aspirin and ibuprofen are COX-2 inhibitors

Aspirin inhibits the antibiotic activity of INH but ibuprofen does not. None of the COX-2 inhibitors alone have effects on bacterial load

38

Mice BALB/C infected with M. tuberculosis H37Rv

Aspirin or ibuprofen + PZA (pyrazinamide)

Aspirin and ibuprofen are COX-2 inhibitors

Reduction of inflammation with ibuprofen or aspirin. Combination of aspirin or ibuprofen with PZA increases the antibacterial effect by reducing the bacterial load on the liver and lung

76

Mice C3HeB/FeJ infected with M. tuberculosis H37Rv

Ibuprofen

COX-2 inhibitor

Ibuprofen decreases the severity of necrotic lesions, reduces bacterial load and increases survival

50

BMDM of mice C57/6BL infected with M. tuberculosis H37Rv

siRNA for COX-2 + PG

COX-2 inhibitor

COX-2 inhibition causes increased bacterial load associated with inhibition of autophagy in infected macrophages

77

BMDM of mice C57BL/6J infected with M. tuberculosis H37Rv

SC-26196

FADS-2 inhibitor

Reduction of inflammation gene transcription (TNF-α, IL-1β, IL-6) and production of reactive oxygen species. Induction of synthesis of new PUFAs for generation of PGE2, PGD2, TXB2, LXA4 and as a nutrient for mycobacteria

44

Plasma of TB patients

Ibuprofeno + conventional treatment

COX-2 inhibitor

Lower amount of PGE2 in patients with ibuprofen. Patients with more PGE2 had reduced radiological lesions, T-cell proliferative response, and secretion of IFN-γ and TNF-α

48

Patients with pulmonary TB

Etoricoxib + conventional treatment

Etoricoxib is COX-2 inhibitor

COX-2 inhibition causes decreased frequency of myeloid-derived suppressor cells (M-MDSCs), necrosis, and disease severity

49

Patients with pulmonary and extra-pulmonary TB

Celecoxib + conventional treatment

Celecoxib is COX-2 inhibitor

Inhibiting COX-2 reduces inflammation by activation of the 5-LOX pathway with reduction of pro-inflammatory cytokines and production of LXA4. Patients with cavities had higher concentrations of LXA4

52

Whole blood form healthy donors infected in vitro with M. tuberculosis H37Rv

Celecoxib + RIF or PZA

Celecoxib is COX-2 inhibitor

COX inhibition decreases T-cell response. Celecoxib alone has no antibacterial effects and its use does not potentiate the effect of antibiotics

79