ORIGINAL ARTICLE Mod Rheumatol (2003) 13:250–255 © Japan College of Rheumatology and Springer-Verlag Tokyo 2003 DOI 10.1007/s10165-003-0231-z Bassel K. El-Zorkany · Geilan A. Mahmoud Hesham A. Shahin · Hosna Moustafa Amira A. Shahin Tumor necrosis factor-alpha and neuropsychiatric lupus erythematosus: relation to single photon emission computed tomography findings Received: May 17, 2002 / Accepted: December 17, 2002 B.K. El-Zorkany · G.A. Mahmoud · A.A. Shahin (*) Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, Department of Rheumatology and Rehabilitation, Faculty of Medicine, Cairo University, Cairo, Egypt Tel./Fax +202-5870668 e-mail: rughe@rusys.eg.net H.A. Shahin Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt H. Moustafa Department of Nuclear Medicine and Radiation Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt Abstract This study was designed to highlight the relation of tumor necrosis factor-α (TNF-α) to neuropsychiatric lupus (NPLE) manifestations. The relation of TNF-α to the type of single photon emission computed tomography (SPECT) findings in this context was also studied. Twenty- one systemic lupus erythematosus (SLE) females, mean age 27.57  9.89 years, and twenty age-matched normal females (controls), were subjected to TNF-α assessment. Different clinical and neuropsychiatric manifestations were evalu- ated. SPECT was carried out for all patients. The results showed that the mean TNF-α level (pg/ml) was significantly raised in patients compared with controls (167.8  102.5 versus 64  50.2, respectively, P  0.005). Thirteen patients (69.1%) had NPLE manifestations. NPLE patients had a significantly higher mean TNF-α than patients without NPLE (203  102.8 versus 109  47.3, respectively, P  0.03). Positive SPECT findings were found in 18 lupus pa- tients (85.7%), including all 13 patients with NPLE (100% sensitivity), with a multiple focal pattern of hypoperfusion being the most frequent type (9/13), followed by diffuse (3/13), and then single focal pattern (1/13). The mean TNF- α was significantly higher in patients with multiple focal pattern (P  0.001). In conclusion, results of this work support the hypothesis that TNF-α could be involved in the pathogenesis of NPLE, and hence, it could be speculated that the evolving anti-TNF therapy can play a potential role in the management of this disease. Key words Neuropsychiatric lupus erythematosus (NPLE) · Neuropsychiatry · Systemic lupus erythematosus (SLE) · Single photon emission computed tomography (SPECT) · Tumor necrosis factor-α (TNF-α) Introduction Systemic lupus erythematosus (SLE) has frequent and po- tentially serious neuropsychiatric (NP) manifestations. The diverse clinical presentations, the relative paucity of infor- mation on clinicopathological correlations, the lack of uniform diagnostic criteria, and the uncertainities about op- timal management are some of the multifaceted dilemmas facing the physician dealing with neuropsychiatric lupus erythematosus (NPLE). 1 Explanations for neurological manifestations in SLE in- clude damage to the nervous system mediated by autoanti- bodies and immune complexes. 2,3 There is also evidence that vascular lesions in patients with SLE, both cerebral and other types, are associated with the occurrence of antiphospholipid antibodies. 4 Another possible pathophy- siological mechanism in NPLE is related to the direct or indirect effect of inflammatory mediators on the nervous system. Proinflammatory cytokines produced both outside and inside the central nervous system (CNS) are known to have dramatic effects on the nervous system, perhaps best described in infections. 5 Earlier studies have reported increased levels of interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon alpha (IFN-α) in cerebrospinal fluid (CSF) of patients with NPLE. 6–8 Tumor necrosis factor-α (TNF-α) is a pluripotent cytokine. It has cytotoxic and antiviral properties, but it exerts its main action through immunological mechanisms. 9 Certain SLE mechanisms are associated with differences in TNF production capacity, and it has been suggested that polymorphic elements within, or linked to, the HLA class II region determine TNF production capacity. 10 Rood et al. 11 found that TNF-308A and HLA-DR3 alleles are indepen- dent susceptibility factors for SLE.