TABLE II.
JAK inhibitors used in animal models of lung inflammation
| Compound | JAK specificity | Route | Species | Allergen/model | Findings | Reference |
|---|---|---|---|---|---|---|
| Tofacitinib | Pan-JAK | Subcutaneous via osmotic minipumps (1.5–15 mg/kg/d) | Mouse | OVA i.p. + alum, then OVA aerosol | Reduced BAL eosinophilia, eotaxin, and IL-13 levels when administered during both sensitization and challenge or during the challenge phase alone | 22 |
| P6 | Pan-JAK | i.p.* | Mouse | OVA i.p. + alum, then OVA aerosol | Decreased airway resistance, BAL eosinophilia, and Muc5AC, but only if PLGA-encapsulated and administered during challenge No effect if administered during sensitization and challenge |
23 |
| R256† | JAK1/3 | Oral gavage (10–50 mg/kg) | Mouse | OVA i.p. + alum then OVA aerosol | Decreased airway resistance, BAL eosinophilia, mucus production Decreased TH2 cytokines only if administered during sensitization |
24 |
| Ruxolitnib | Pan-JAK | Intragastric (180 mg/kg)‡ | Mouse | OVA + low-dose LPS inhaled then OVA aerosol | Reduced BAL eosinophil, neutrophil, and IL-17 levels | 25 |
| iJak-381 | JAK1 | i.n., dry powder inhaler | Mouse Guinea pig | OVA i.p. + alum then OVA aerosol Aspergillus, Alternaria, and house dust mite (AAH) | Reduced BAL eosinophilia, CCL11, airway resistance, and Muc5AC in OVA-challenged mice Reduced BAL eosinophilia, neutrophilia, CCL11, and CXCL1 in in AAH-challenged mice Reduced lung inflammation in OVA-challenged guinea pigs |
18 |
| LAS194046 | Pan-JAK§ | i.t. (0.3–1 mg/kg) | Rat | OVA i.p. + alum then OVA aerosol | Reduced BAL eosinophilia and neutrophila, and AHR (Penh) | 16 |
| iJAK-001 | Not stated | i.t. (0.03–1 mg/kg) or dry powder inhaler (10 mg) | Rat Sheep | Alternaria extract i.t. Ascaris suum | Reduced Alternaria-induced BAL eosinophilia in mice Reduced Ascaris-induced airway resistance in sheep |
19 |
| Tofacitinib | Aerosol (1–2 mg/kg) | Mouse | House dust mite extract | Reduced eosinophil and total protein levels | 26 | |
| Tofacitinib | i.p. (5 mg/kg) | Mouse | OVA i.p. + alum then OVA i.n. | Reduced numbers of tissue eosinophils, polypoid-like lesions, TH2 cytokines, and phospho- STAT6 | 27 |
AAH, Aspergillus, Alternaria, and house dust mite; i.n., intranasal; i.p., intraperitoneal; i.t., intratracheal, PLGA, poly d,l-lactic-co-glycolic acid.
*
Alone (3 mg/kg) or in PLGA-encapsulated nanoparticles (60 mg/kg).
†
This compound is apparently now known as AZD0449.
‡
Timing of ruxolitinib administration is not clear.
§
This compound was also found to inhibit Flt3 and TrkA.