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The regulation of T helper (Th)1‐ and Th2‐type cytokine patterns is important in the final outcome of leishmaniasis in human and murine models. We examined the efficacy of garlic therapy or a combination of garlic and an antimonial drug (glucantime) in promoting healing and regulation of Th1/Th2 cytokine patterns in highly susceptible BALB/c mice infected with Leishmania major. Separate groups of infected mice received 20 mg/kg/day garlic, 60 mg/kg/day glucantime or a combination of the two, from day 30 after infection for 2 weeks. An enzyme‐linked immunosorbant assay ( ELISA) was performed on spleen cell culture supernatants for interferon(IFN)‐γ interleukin(IL)‐2, IL‐4 and IL‐10. The results indicate that garlic therapy is more effective than the usual antileishmanial drug in curing the infection. Garlic‐treated mice developed Th1‐type cytokine responses. In contrast, glucantime therapy led to a Th2‐type response in the control group with a lower level of IL‐2. However, a combination of garlic and glucantime treatment was more effective than either treatment alone, and resulted in a Th1‐type response similar to that which developed with garlic treatment. These results suggest that garlic extract in combination with an antimonial drug, may provide effective therapy against L. major. The immunomodulatory properties of garlic were elucidated in terms of shifting the cytokine response to a Th1‐type pattern and therefore causing the protective response.

Although migraine affects about 15% of population and many studies have been performed to find the mechanism and a successful management, the physiopathology of migraine is still largely unknown. The possibility of an immunoglobulin E (IgE)-mediated allergic mechanism and the role of histamine remain controversial.The aim of the present study was to evaluate serum total IgE and histamine levels in migraine patients and the influence of allergy on them.Seventy patients (18±58 years) with migraine without aura were divided into two groups according to their history of allergy (60% with and 40% without allergy). Serum samples were collected during fasting without allowing any premedication during the two periods of attack and remission. There was a control group containing 45 healthy volunteers. Serum total IgE and histamine levels were measured by enzyme-linked immunosorbent assay and fluorimetric methods, respectively.Mean and standard errors of serum histamine (ng/ml) and total IgE (IU/ml) levels were found in the control group to be 48.16 AE 2.70 and 38.31 AE 3.20, in the migraine with allergy group 159.11 AE 4.60 and 303.30 AE 42.50 and in the migraine without allergy group 105.01 AE 8.50 and 79.07 AE 2.70, respectively.Total IgE levels in migraine with allergy group were found to be significantly (P < 0.0001) above that in the control and another group, suggesting an influence of an IgE-mediated mechanism on migraine. Although the plasma histamine levels, which were significantly elevated (P < 0.0001) in patients with migraine, both during headache and symptom-free periods, when compared with the control group, indicate that there is an increased susceptibility to histamine in allergic conditions, this molecule has also an unrelated role in migraine.The relationship between allergy and migraine can be based, in part, on an IgE-mediated mechanism, and histamine release plays an important role.Thus, the avoidance of allergic conditions in migraine patients may be a simple, helpful way for prophylaxis or their treatment.

Opioids can induce analgesia and also hyperalgesia in humans and in animals. It has been shown that systemic administration of morphine induced a hyperalgesic response at an extremely low dose. However, the exact mechanism(s) underlying opioid-induced hyperalgesia has not yet been clarified. Here, we have investigated cellular events involved in low-dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 microg i.t.) could elicit hyperalgesia as assessed by the tail-flick test. G(alphas) mRNA and protein levels increased significantly following exposure to the hyperalgesic dose of morphine. Furthermore, morphine at an analgesic dose (20 microg i.t.) significantly decreased cAMP levels in the dorsal half of the lumbar spinal cord, whereas the tissue cAMP levels were not affected by morphine treatment at a hyperalgesic dose. Intrathecal administration of nifedipine, an L-type calcium channel blocker, antagonized the hyperalgesia induced by the low-dose of morphine. Furthermore, pretreatment with the selective protein kinase C (PKC) inhibitor chelerytrine resulted in prevention of the morphine-induced hyperalgesia. KT 5720, a specific inhibitor of protein kinase A (PKA), did not show any effect on low-dose morphine-induced hyperalgesia. These results indicate a role for G(alphas), the PLC-PKC pathway, and L-type calcium channels in intrathecal morphine-induced hyperalgesia in rats. Activation of ordinary G(alphas) signaling through cAMP levels did not appear to play a major role in the induction of hyperalgesia by low-dose of morphine.

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