Protective Role of JAK Inhibitor in Rat Sepsis

Abstract

Acute lung injury (ALI) is a critical condition marked by inflammation-induced lung swelling, resulting in acute hypoxic respiratory failure. The JAK inhibitor tofacitinib has been implicated in the regulation of inflammatory responses. In this study, we hypothesized that the JAK inhibitor tofacitinib could modulate neutrophil infiltration in a lipopolysaccharide (LPS)-induced sepsis mouse model.

A total of 18 rats (8 weeks old, weight 220–250 grams) were randomly divided into three groups (n = 6 per group): Control group – received intraperitoneal normal saline. LPS group – received 30 mg/kg of LPS intraperitoneally. Tofacitinib + LPS group – received 30 mg/kg of the selective JAK inhibitor tofacitinib intraperitoneally, 15 minutes before LPS administration.

After 24 hours, the animals were euthanized. Inflammatory cell infiltration and levels of proinflammatory cytokines— TNF-α, IL-1β, IL-6, bacterial CFU and myeloperoxidase (MPO) activity—were assessed.

Compared to the LPS group, pretreatment with tofacitinib significantly reduced MPO activity, TNF-α, IL-1β, bacteria CFU in blood and IL-6 levels. Notably, inflammatory cell migration and infiltration were suppressed, as shown by decreased MPO activity in treatment group, P<0.05. Similarly, IL-6, bacteria CFU concentrations in the treatment group were significantly lower than in the LPS group.

These findings suggest that tofacitinib exerts protective and anti-inflammatory effects in LPS-induced ALI, potentially offering a therapeutic approach for managing sepsis-related lung injury.