Table 1: Effect of eicosanoid supplementation during M. tuberculosis H37Rv infection.

Mouse strain/model

Eicosanoid administered

Treatment

Main effects

Ref.

SV129 and deficient in 5-LOX

LTB4 single treatment

In vivo

LTB4 induces IFN-γ, decreasesTNF-α, promotes necrosis and increases pathogenicity and mortality. IncreasesTNF-α in 5-LOX deficient mice

19

C57BL/6

PGE2 single treatment

In vivo

PGE2 reduces excess of IFN-γ, necrosis and pulmonary damage and does not interfere with the action of antibiotics

37

C3HeB/FeJ

Iron-enriched diet + AIN-93G (EPA/DHA supplement)

In vivo

EPA/DHA + iron causes decreased IL-1, TNF-α and IFN-γ and increased bacterial load. Supplements alone decrease inflammation and anemia. EPA/DHA decreases bacterial load, increases SPM and T-cell recruitment

64

C3HeB/FeJ

Enriched EPA/DHA diet + rifafour + RIF (rifampicin)-INH (isoniazid)

In vivo

EPA/DHA-enriched diet reduces the production of pro-inflammatory cytokines (IFN-γ IL-1β, IL-6, IL-1α). The EPA/DHA diet elevates SPM, reduces pro-inflammatory lipids, and decreases pulmonary damage

74

Monocytes from TB patients and healthy individuals treated with ibuprofen

PGE2

Ex vivo/in vitro

PPGE2 reduces IFN-γ and TNF-α, expression of surface receptors (SLAMF1, CD31, CD46, CD80, CD86, MHC1) necessary for T cell activation and receptors (SLAMF1, PD-L1) in neutrophils. PGE2 protects the host from excessive inflammation and promotes autophagy

69

MDM from healthy donors

PGE2, EP2 or EP4 receptor blockers or agonists

In vitro

Treatment with EP2 agonists results in lower cell necrosis. Treatment with EP4 antagonists results in COX-2 inhibition

67

Monocytes from healthy donors

AA Analogs

In vitro

AA analogs induce cell death by both apoptosis and necrosis. Necrosis induced by AA derivatives in monocytes requires calcium mobilization, production of reactive oxygen species, calcium modulating enzymes, PLA2 and calpains

53

Blood mononuclear cells from donors of unknown status

Short-chain fatty acids (AG) (C4)

In vitro

Short-chain AGs do not affect COX-2 expression, but decrease IL-10 and Th17 proliferation

54

MDM from healthy donors

RvD1, RvD2, PDX, LXA4 or Mar1 without conventional treatment

In vitro

RvD1, LXA4 and Mar1 reduce TNF-α production. RvD1 and Mar1 induce anti-inflammatory and antimicrobial mechanisms and NFκB translocation. RvD1 and PDX increase phagocytosis

25

All experiments carried out with different bacterial loads. All treatments administered in different post-infection regimens. Rifafour (150 mg rifampicin + 75 mg isoniazid + 400 mg pyrazinamide + 275 mg ethambutol).