Interleukin-2 gene expression in different phases of episodic cluster headache--a pilot study.

BACKGROUND: The pathophysiology of cluster headache (CH) is still largely unknown. Immunological mechanisms have been suggested to be of importance. AIM: This study aimed to investigate cytokine interleukin-2 (IL-2) as a possible marker of immune system involvement in the pathophysiology of CH. METHODS: Eight episodic patients with CH and 16 healthy headache-free control subjects matched for age and gender were studied. Venous blood samples were drawn from the patients with CH on three occasions; during active period between headache attacks, during an attack and in remission. Venous blood samples were drawn once from each control subject. We analysed IL-2 gene expression, using quantitative real-time polymerase chain reaction. RESULTS: Patients with CH had significantly increased relative IL-2 gene expression levels between headache attacks during active CH period (median 9.9 IL-2 cDNA/glyceraldehyde-3-phosphate dehydrogenase cDNA; IQR 6.2-10.3) compared to during attacks (median 2.8; IQR 0.7-3.2, P = 0.012), remission (median 1.6; IQR 0.9-1.8, P = 0.017) and controls (median 0.9; IQR 0.6-1.9, P = 0.0001). CONCLUSION: The increment of IL-2 found during the active CH period may support a role for this cytokine and subsequently for the immune system in the pathophysiology of CH. An expansion of this study to a broader group of cytokines and a larger patient cohort is warranted.

Comparison of soluble ICAM-1, VCAM-1 and E-selectin levels in patients with episodic cluster headache and giant cell arteritis.

The pathophysiology of cluster headache (CH) is supposed to involve the lower posterior part of the hypothalamus, the trigeminal nerve, autonomic nerves and vessels in the orbital/retro-orbital region. The exact connection of this hypothalamic-trigemino-autonomic-vascular axis is not fully understood. The presence of inflammation in the perivascular tissue of the retro-orbital region has been presented as a possible mechanism behind the pain and the sympatheticoplegia sometimes observed during headache attacks. In a previous study we found neither increased levels of erythrocyte sedimentation rate, C-reactive protein or acute-phase reactants nor clinical signs of a generalized inflammatory disorder. However, these tests may not be sensitive enough to detect a focal inflammatory process in the retro-orbital region. In the present study, we analysed serum levels of three soluble adhesion molecules; soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin) in patients with episodic CH and in patients with biopsy-positive giant cell arteritis (GCA), a known vasculitic disorder of large and medium-sized arteries. A control group of healthy volunteers was also included. Within the CH group, sICAM-1, sVCAM-1 and sE-selectin showed an increasing trend in remission compared with the active CH period, but the difference was statistically significant for sE-selectin only. The mean sICAM-1 value was higher in patients with active GCA than in CH patients during the active cluster period. Compared with the healthy control group, the mean levels of soluble adhesion molecules in CH patients also tended to be higher, but statistically significantly so only for sVCAM-1. We hypothesize that CH is not a vasculitic disorder of the medium-sized arteries, but CH patients may have an immune response that reacts differently from that of healthy volunteers.