Cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) disorders was assayed for cytokines, prostaglandins, and autoantibodies. CSF interleukin-6 (IL-6) in patients with CNS infection (374.24 +/- 92.61 pg/mL) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (71.40 +/- 5.89 pg/mL) were significantly higher than in patients with CNS inflammation (33.92 +/- 29.36 pg/mL) or controls (non-inflammatory CNS diseases) (4.35 +/- 3.00 pg/mL). Interleukin-1 beta, interferon alpha, and tumor necrosis factor alpha were undetectable in these samples: CSF prostaglandin E2 (PGE2) also exhibited similar patterns as IL-6. CSF immunoglobulin G (IgG) in patients with NP-SLE (8.84 +/- 1.80 mg/dL) was much higher than in patients with CNS infection (4.65 +/- 3.09 mg/dL), CNS inflammation (2.54 +/- 1.24 mg/dL), or controls (2.11 +/- 1.03 mg/dL). CSF autoantibodies against calf thymus antigens were present in patients with NP-SLE but not in patients with CNS infection as demonstrated by immunoblot. These results suggest that high IL-6 and PGE2 in CSF favors the diagnosis of CNS infection, while modestly elevated IL-6, high IgG, and autoantibodies against calf thymus antigens in CSF are the features of NP-SLE.