Limited efficacy of pentoxifylline as anti-inflammatory agent in experimental pneumococcal meningitis

• Published in: Clinical and experimental immunology 1997-03, Vol.107 (3), p.458-461
• Main Authors: ZYSK, G, BRÜCK, W, FISCHER, F. R, MÄDER, M, RIECKMANN, P, NAU, R
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cell Movement - drug effects; Interleukin-1 - antagonists & inhibitors; Interleukin-1 - biosynthesis; Leukocytes - drug effects; Medical sciences; Meningitis, Pneumococcal - cerebrospinal fluid; Meningitis, Pneumococcal - drug therapy; Meningitis, Pneumococcal - pathology; Pentoxifylline - pharmacology; Pentoxifylline - therapeutic use; Pharmacology. Drug treatments; Rabbits; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - biosynthesis; Streptococcus pneumoniae; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1997.d01-949.x

Dexamethasone appears to show some adverse side-effects as adjunctive anti-inflammatory agent in bacterial meningitis. For this reason, we tested the anti-inflammatory and neuroprotective effect of pentoxifylline administered 15 min before starting antibiotic treatment with ceftriaxone (n = 10) versus antibiotic therapy alone (n = 9) in the rabbit model of pneumococcal meningitis. Pentoxifylline lowered the medians of leucocyte density, tumour necrosis factor-alpha (TNF-alpha) and lactate in the cerebrospinal fluid (CSF), but only leucocyte migration into the subarachnoid space was significantly inhibited 8 h after initiation of therapy (P = 0.01). CSF protein, brain water content, and the entry of ceftriaxone into CSF were not influenced by pentoxifylline. The density of neuronal apoptoses in the dentate gyrus was slightly lower in animals receiving pentoxifylline than in those treated with ceftriaxone only. The median concentration of neuron-specific enolase in CSF was lower in the pentoxifylline-treated group, but the difference was not significant. In conclusion, pentoxifylline showed some anti-inflammatory activity in pneumococcal meningitis, but the substance failed significantly to reduce neuronal damage.