Letter to the Editor No significant difference in cytokine levels in patients with restless legs syndrome versus controls – Preliminary data To the Editor The prevalence of restless legs syndrome (RLS) has been found to be significantly higher in certain immuno- logical diseases such as multiple sclerosis and rheumatoid arthritis [1,2] than in the general population. Various cytokines have been used as an indicator and marker of severity in these immunological disorders [3,4]. We measured the blood levels of cytokines in patients with RLS. The patients remained on RLS medications to insure adequate sleep. Patients with any other diseas- es or medications that raise the level of cytokines were excluded from the study. The patients and controls were asked to maintain a sleep log for one week prior to the drawing of blood. The patients also completed the Inter- national Restless Legs Syndrome Severity Scale (IRLS) [5] as well as a Visual Analogue Scale (VAS). Blood samples were obtained from patients and controls at about 10 am. The samples were analyzed blindly at Ani Lytics Incorporated, Gaithersburg, MD. The following cytokine levels were measured: Interferon gamma, TNF alpha, IL1B, IL 6, IL12 and IL 4. Twenty-five patients were screened from the RLS clinic and six patients were excluded for smoking, Parkinson’s disease, insomnia and corticosteroid ingestion. We col- lected blood samples from 19 patients who fulfilled the inclusion criteria and 16 controls. We selected 11 pa- tients (6 men, 5 women, average age = 51.54 years) and 11 controls (6 men, 5 women, average age = 51.24 years) matched for age, sex, total sleep time (TST) based on subjective estimation and other medical conditions (Table 1). The patients were then subgrouped into those on dopaminergic agents and those on non-dopaminergic agents. The two patient subgroups and controls were also matched for age, sex, TST and other medical conditions. We did not find any statistically significant difference in the levels of the six cytokines in the 11 patients vs the 11 controls (Tables 1 and 2) nor in five RLS patients treated with dopaminergic agents and the six RLS patients treated with non-dopaminergic agents. There was no correlation between any of the cytokine levels and severity of RLS as determined by the IRLS scale, its Symptom and Impact subscales or the VAS. The results were similar when the RLS patients with only a family history were analyzed separately. Future studies need to address other immunological factors like TCD4 lymphocytes and TCD8 lymphocytes. Table 1 Levels of cytokines and medications in the RLS patients S. no Age Sex TST (hours) IRLS VAS (inches) INFG (pg/ml) TNFA (pg/ml) IL1B (pg/ml) IL6 (pg/ml) IL12 (pg/ml) ILIV (pg/ml) RLS medications 1 53 F 9 0 0 0.00 0.00 0.00 0.47 84.62 0.00 Ropinirole, tramadol 2 51 M 5.8 27.5 0.25 36.80 0.00 0.00 1.54 147.65 0.00 Pramipexole, clonazepam 3 59 F 7 21.5 0 0.00 0.00 0.00 2.52 9.07 0.00 L-dopa 4 49 F 7.2 8 0 20.10 0.00 0.00 1.00 0.73 16.00 Pramipexole 5 66 F 5 NA NA 53.20 0.00 0.00 4.80 45.00 0.00 Pramipexole, oxycodone 6 37 M 6.3 17 0 0.00 0.00 0.00 3.28 51.23 5.50 Gabapentin 7 54 M 8.1 5 0.2 0.00 0.00 0.00 0.93 0.00 0.00 Clonazepam 8 49 M 4.1 30.5 3 0.00 0.00 0.00 0.62 11.58 0.00 Oxycodone, alprazolam 9 34 F 6.3 25 1.9 11.80 0.00 0.00 0.62 0.00 50.30 Ferrous sulfate 10 57 M 7.1 23 0 0.00 0.00 0.00 6.71 0.00 0.00 Oxycontin 11 58 M 5.7 26 2.6 4.20 0.00 0.00 0.93 32.45 0.00 Tramadol, gabapentin AVG. 51.55 6.51 18.35 0.72 11.46 0.00 0.00 2.13 34.76 6.53 Patients 1–5 are those on dopaminergic agents. TST, total sleep time; IRLS, international RLS rating scale; VAS, visual analogue scale; INFG, interferon gamma; TNFA, tumor necrosis factor alpha; IL1B, interleukin 1B; IL6, interleukin 6; IL12, interleukin 12; ILIV, interleukin 4. 1389-9457/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2006.07.296 www.elsevier.com/locate/sleep Sleep Medicine 8 (2007) 98–99