45,56,57 In recent years, immunological

research in TS has focused on cytokines. In a recent prospective longitudinal study, increased serum levels of the cytokines interleukin (IL)-12 and tumor necrosis factor (TNF)-oc in juvenile TS patients were observed.58 During exacerbations of tics, a further increase in IL-12 and TNF-oc was observed, pointing to a relationship between tic severity and proinflammatory cytokines. In OCD, however, decreased levels of TNF-ot were described.59-61 Since OCD and TS show a high rate of comorbidity, a possibly discriminative marker – decreased in OCD and increased Inhibitors,research,lifescience,medical in TS- would be very valuable. Although the results of the kynurenine estimations in TS are divergent, depending on interfering factors,62,63 Enzalutamide order changes in the kynurenine levels in the sera of TS patients also point to the involvement of the immune system. Kynurenine is the product of activated monocytes/ macrophages; changes in kynurenine production take place during Inhibitors,research,lifescience,medical inflammatory processes. Moreover, kynurenine and other products of the tryptophan/kynureninemetabolism are neuroactive proteins, possibly themselves contributing to changes in neurotransmitter metabolism. Moreover, increased levels of the soluble adhesion molecules Inhibitors,research,lifescience,medical V-CAM-1 and E-selectin – increased in inflammatory states – were reported in children and adults suffering from TS.64 A case report of successful

Inhibitors,research,lifescience,medical treatment with a cyclo-oxygenase (COX)-2 inhibitor also promotes the view that an inflammatory process is involved in TS.65 Inflammation in TS as e result of an infectious or postinfectious process It has been described that tics appear or are exacerbated in acute Lyme disease,66 infection with Mycoplasma pneumoniae,67,68 or acute streptococcal infection.69 Moreover, an association of the common cold with tic disorders has been observed.63 Improvement or remission of the tics has been

Inhibitors,research,lifescience,medical associated with antibiotic therapy.65,66,68 These findings strongly suggest that infectious agents contribute to the pathogenesis of tics and TS. PANDAS70,71 has been extensively described during recent years. The main symptoms of PANDAS are motor and vocal tics and OC behavior like that found in TS.72 Although crossreacting antibodies against the putamen have been observed in PANDAS,73 the mechanism has not yet been established. TS is proposed to be STK38 a part of PANDAS. Increased antibody titers and other features of PANDAS, however, have also been described in adult TS patients,74,75 while the PANDAS concept is restricted to children. Antibodies against certain streptococcal M proteins, ie, proteins on the surface of streptococci which are known to be responsible for the virulence and the immune properties of the particular streptococcal strain, are increased in children and adult TS patients.