Figure 1.

IL-1β plays a greater role in mediating lung permeability increase and hypoxemia than IL-1α. (A–E) The effect of conventional IL-1α deficiency in two-hit lung injury model. (F–J) The effect of intratracheal (i.t.) anti-IL-1α monoclonal antibody (αIL-1α) treatment in two-hit lung injury. (K–O) The effect of i.t. anti-IL-1β monoclonal antibody (αIL-1β) treatment in two-hit lung injury. (A,F,K) Study protocol. Mice were anesthetized and placed on high volume mechanical ventilation (HVV) with tidal volumes of 30 ml/kg with 3 cmH₂O positive end-expiratory pressure (PEEP) for 2.5 h. Antibodies (2.5 μg/g) were administered i.t. at the same time with i.t. LPS. (B,G,L) Arterial partial pressure of oxygen (PaO₂). PaO₂ was measured at 30 and 150 min after starting MV. (B,L) **indicates significant difference (adjusted P < 0.01), determined by two-way ANOVA followed by Sidak's multiple comparisons test. (G) No significance was detected in PaO₂ control lgG and αlL-1α mice by two-way ANOVA followed by Sidak's multiple comparisons test. (C,H,M) Lung permeability determined by albumin in BALF. (D,l,N) Absolute counts of neutrophils and macrophages in BALF. (E,J) IL-1β or (O) IL-1α levels determined in BALF. (C,D,M) *,***indicates P < 0.05, and P < 0.001, respectively, determined by Mann-Whitney U-test. N.S., not significant.