Table 2. SPMs influence host defence and infectious inflammation.
| Infection or infective agent | Mediator | Role | Refs |
|---|---|---|---|
| Virus | |||
| Influenza A | Lipoxins | H5N1, a more virulent strain, is associated with a decrease in lipoxin signalling leading to increased leukocyte recruitment and extrapulmonary dissemination of the virus | 98 |
| Protectins | Protectin D1 is suppressed in virulent H5N1; treatment with protectin D1 improves survival | 102 | |
| RSV | Lipoxins | Lipoxins are required to elicit alternatively activated macrophages, leading to resolution of lung pathology | 106 |
| HIV | Lipoxins | Lipoxins are produced in HIV infection, but their function is uncertain | 163 |
| HSV | Resolvins | Reduce neutrophil and CD4+ T cell recruitment (TH1 cells and TH17 cells), increase IL-10 and decrease pro-inflammatory cytokines and stromal keratitis lesions | 107 |
| Protectins | Reduce neutrophil and CD4+ T cell recruitment (TH1 cells and TH17 cells), increase IL-10 and decrease pro-inflammatory cytokines and stromal keratitis lesions | 108 | |
| Bacterial infection | |||
| Mycobacterium tuberculosis | Lipoxins | 5-lipoxygenase deficient mice have lower circulating levels of LXA4, increased TH1-type inflammation and lower rates of resistance | 92 |
| LXA4 associates with plasma membrane repair and necrosis of infected macrophages | 164,165 | ||
| Mycobacterial susceptibility is linked to LTA4 hydrolase activity that controls LTB4 production directly and LXA4 production indirectly | 15 | ||
| Variations in the ALOX5 gene (which encodes 5-lipoxygenase) are associated with variation in tuberculosis susceptibility | 93 | ||
| Periodontitis | Lipoxins | In rabbits, overexpression of lipoxin or treatment with a lipoxin analogue decreases bone loss and tissue inflammation | 85 |
| Decrease PMN infiltration to sites of Porphyromonas gingivalis infection | 84 | ||
| LXA4 analogue promotes regeneration of hard and soft tissue loss in pig models of periodontitis | 166 | ||
| Resolvins | Resolve local inflammation and promote tissue regeneration after infection-mediated destruction | 61 | |
| Decrease inflammation and protect against bone loss | 87 | ||
| Decrease neutrophil infiltration and pro-inflammatory cytokine levels | 88 | ||
| Restore impaired phagocyte activity of macrophages | 90 | ||
| RvE1 is bone-protective in murine models, mediating preservation and accelerating regeneration | 167 | ||
| Salmonella spp. | Lipoxins | Increase BPI and enhanced bacterial killing | 79 |
| Gram-negative bacteria-associated sepsis | Lipoxins | Decrease pro-inflammatory mediators via NF-κB mediated mechanism, decrease bacterial load and increase peritoneal macrophages and survival | 96 |
| Decrease PMN recruitment, attenuate inflammation and, in combination with antibiotics, improve survival | 95 | ||
| Resolvins | Decrease bacterial burden, limit cytokine production, increase macrophage phagocytosis and improve survival | 14 | |
| Decrease antibiotic requirements, enhance actions of ciprofloxacin and accelerate resolution | 12 | ||
| Burn-associated sepsis | Resolvins | Enhance and/or restore neutrophil recruitment and improve overall survival | 168 |
| Escherichia coli (pneumonia and ARDS) | Lipoxins | Promote apoptosis of neutrophils | 80 |
| Resolvins | Decrease neutrophil recruitment, enhance bacterial clearance, decrease IL-1 and IL6, and improve survival | 13 | |
| Enhance neutrophil apoptosis and improve survival | 81 | ||
| Staphylococcus aureus | Resolvins | Enhance vancomycin-mediated clearance of bacteria | 12 |
| Borrelia burgdorferi | Lipoxins | In the absence of 5-lipoxygenase, mice develop persistent arthritis | 91 |
| Parasites | |||
| Toxoplasma gondii | Lipoxins | Infected mice have high serum levels of lipoxins | 115 |
| 5-lipoxygenase deficient animals have higher levels of IL-12 and IFNγ with improved parasite control but have higher mortality from excess inflammation | 111 | ||
| LXA4 suppressed IL-12 production in dendritic cells | 110 | ||
| Trypanosoma cruzi | Lipoxins | Aspirin-triggered lipoxins are elevated, and increased 15-epi-LXA4 levels improve parasite load, cardiac inflammation and mortality | 114 |
| Plasmodium spp. (malaria parasite) | Lipoxins | 5-lipoxygenase deficient mice have higher levels of IL-12 and IFNγ and increased mortality. Treatment with lipoxins decreases brain inflammation and improves survival | 113 |
| Angiostrongylus costaricensis | Lipoxins | Treatment of infected rats with an LXA4 analogue shortens the duration of the allergic response to the parasitic infection | 112 |
| Yeast | |||
| Candida albicans | Resolvins | Reduces neutrophil chemotaxis, enhances phagocytosis and promotes clearance | 117 |
ARDS, acute respiratory distress syndrome; BPI, bactericidal permeability-increasing protein; HSV, herpes simplex virus; IFNγ, interferon-γ; IL, interleukin; LT, leukotriene; LXA4, lipoxin A4; NF-κB, nuclear factor-κB; PMN, polymorphonuclear leukocyte; RSV, respiratory syncytial virus; RvE1, resolvin E1; SPM, specialized pro-resolving mediator; TH, T helper.