Cytokine and C-reactive protein concentrations over 6 months of treatment with clozapine in treatment resistant schizophrenia

Brain Behav Immun Health. 2026 Sep 1;56:101342. doi: 10.1016/j.bbih.2026.101342. eCollection 2026 Oct.

ABSTRACT

Clozapine may have both pro- and anti-inflammatory effects, which could contribute to its unique efficacy in treatment resistant schizophrenia (TRS). Increases in pro-inflammatory cytokines occur during the first weeks after clozapine initiation, but the changes occurring over longer periods of clozapine administration are largely unknown. This study examined C-reactive protein (CRP), tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and interleukins (IL) IL-2, IL-4, IL-6, IL-8, IL-12p70 and IL-13 prior to clozapine titration (baseline) and after 3 and 6 months of clozapine treatment in TRS. Symptom severity was assessed at the same time-points. Data were available in 53 individuals at baseline, 34 individuals at 3 months and 28 individuals at 6 months. Following correction for false discovery rate (FDR): significant effects of time were observed for IL-10 (F(2, 67.7) = 9.15, P < 0.001, q = 0.010) and TNF-α (F(2, 58.9) = 5.67, P = 0.006; q = 0.030), related to significant increases in both IL-10 and TNF-α at 3 and 6 months after commencing clozapine compared to at baseline (α = 0.05). There were no significant associations between temporal changes in peripheral inflammatory marker concentrations and changes in total symptom severity, or relationships between inflammatory marker concentrations at baseline and total symptom severity at 3 months. Concurrent increases in TNF-α and IL-10 may reflect increased activation of both pro-inflammatory and compensatory anti-inflammatory mechanisms over 6 months of clozapine treatment. Composite indices of inflammatory profile may be advantageous in future studies examining relationships with symptom improvement during clozapine treatment.

PMID:42733424 | PMC:PMC13571128 | DOI:10.1016/j.bbih.2026.101342