Anti-interleukin-6 antibodies attenuate inflammation in a rat meningitis model.

Abstract

Interleukin-6 (IL-6) is elevated in the cerebrospinal fluid (CSF) of humans and animals with bacterial meningitis. This study's hypothesis was that anti-IL-6 antibodies will attenuate meningeal inflammation in a rat model of bacterial meningitis. 14 male Sprague-Dawley rats were inoculated intracisternally (IC) with 0.1 mL of heat-killed pneumococci. At one hour post-inoculation, the rats received intraperitoneal doses of either 1.0 mL phosphate-buffered saline (PBS treatment group, n = 7) or 70 microg anti-IL-6 antibodies in 1.0 mL PBS (anti-IL-6 antibody treatment group, n = 7). Nine rats (normal group, n = 9) had no inoculation, and four rats (surgical sham group, n = 4) had IC inoculations of saline. At six hours post-inoculation, all the animals had CSF removed via IC tap. The CSF protein and white blood cell (WBC) count measures were compared using a t-test. Mean CSF WBC for the anti-IL-6 treatment group was 2,458/microL, versus the PBS controls' mean of 9,697/microL (p = 0.007). Mean CSF protein for the anti-IL-6 group was 180 mg/dL, versus 296 mg/dL for the controls (p = 0.032). The surgical sham and normal animals had normal CSF WBC and protein values. In this rat meningitis model, systemic treatment with anti-IL-6 antibodies after the induction of meningitis suppressed both CSF WBC count and CSF protein level, two important indices of meningeal inflammation.