ICAM-1 and CD11b inhibition worsen outcome in rats with E-coli pneumonia

ICAM-1 and CD11b inhibition worsen outcome in rats with E. coli pneumonia. J. Appl. Physiol. 87(1): 299-307, 1999.-We investigated whether inhibiting an endothelial adhesion molecule [intracellular adhesion molecule 1 (I:CAM- 1)] would alter outcome and lung injury in a similar fashion to inhibition of a leukocyte adhesion molecule (integrin CD11b) in a rat model of gramneg ative pneumonia. Inhibition of ICAM-1 with monoclonal antibody (MAb) 1A29 ( 1 mg/kg sc or 0.2 or 2 mg/kg iv, q 12 h x 3) or of CD11b with MAb 1B6 ii mg /kg sc, q 12 h x 3) were compared against similarly administered placebo pr oteins in rats challenged with intrabronchial Escherichia coli. After chall enge, all animals were treated with antibiotics, ICAM-1 MAb (6 mg/kg, iv, t otal dose) increased mortality vs. control (P = 0.03). CD11b MAb (3 mg/kg, sc, total dose) did not significantly (P = 0.16) increase mortality rates, but this was not in a range of probability to exclude a harmful effect. All other doses of MAb had no significant effect on survival rates. ICAM-1 and CD11b MAbs had significantly different effects on the time course of lung injury, circulating white cells and lymphocytes, and lung lavage white cell s and neutrophils (P = 0.04-0.003). CD11b MAb decreased, whereas ICAM-1 MAI D increased these measures compared with control from 6 to 12 h after E. co li. However, from 144 to 168 h after E. coli both MAbs increased these meas ures compared with control rats but to a greater: level with CD11b MAb. Thu s both ICAM-1 and CD11b appear to be necessary for survival during E. coli pneumonia. Although these adhesion molecules may participate differently in early lung injury, with CD11b increasing and ICAM-1 decreasing inflammatio n and injury, both are important for the resolution of later injury. During gram-negative pneumonia the protective roles of ICAM-1 and CD11b may make their therapeutic inhibition difficult.