| First Author | Naderi A | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 12 | Pages | 105520 |
| PubMed ID | 36404927 | Mgi Jnum | J:331383 |
| Mgi Id | MGI:7387794 | Doi | 10.1016/j.isci.2022.105520 |
| Citation | Naderi A, et al. (2022) Beneficial effects of CCL8 inhibition at lipopolysaccharide-induced lung injury. iScience 25(12):105520 |
| abstractText | CCL8 (MCP-2) is a chemoattractive cytokine associated with various immune-related pathologies. Recent studies show that CCL8 is significantly stimulated during acute respiratory distress syndrome in severely ill patients with COVID-19, making the inhibition of CCL8 activity a promising treatment. Lipopolysaccharide (LPS)-induced lung injury was evaluated in mice using a neutralizing antibody (1G3E5) against human CCL8. Pharmacokinetic studies indicated that following IP administration, 1G3E5 was sustained at higher levels and for a longer period compared to IV administration. CCL8 expression in the lungs was not enhanced by LPS, but CCR2 and CCR5 receptors were significantly stimulated. 1G3E5-mediated inhibition of CCL8 was associated with the reduction of pulmonary inflammation and suppression of various pro-inflammatory cytokines. These results point to a previously unrecognized, permissive role for CCL8 in mediating cytokine induction and ultimately sustaining inflammation. Disruption of CCL8 activity may provide a strategy for mitigating pulmonary inflammation during lung injury when related to abnormal cytokine induction. |
