Hypothesis IL-1 may mediate the epidemiological relationship between HH and cancer progression link between the psychological factors and the biological effects. IL1: lymphocyte proliferation, participates in many 'good' processes. If IL1 is blocked in the brain, mice do not develop helplessness! If put in a new situation with controllable stress: The mice who could escape the shock will learn the fastest The one's with learned helplessness just sit at the side. They don't try to stop it, they believe they can't. When they are given a IL1 blocker, they started to behave as if they came from the IS group could be entirely reversed! What does brain IL-1 do to cancer? Animals were injected with a peripheral tumour: Half were given IL-1 in the brain, half placebo Brain-IL-1 led to more metastases in the lungs than placebo. DUS: more IL1: more metastasis, aside from more HH! This was blocked by a beta-blocker, Nadolol Is helplessness associated with peripheral IL-1? A few studies showed that uncontrollable stress caused elevated levels of peripheral IL-1. More than other cytokines, IL-1 responds to this type of stress! If it causes more metastasis, it could be an important factor!! Is IL-1 associated with cancer-promoting events? Angiogenesis IL-1 plays a role in increasing IL-8 and VEGF Helplessness was positively correlated with VEGF in ovarian-cancer patients IL-8 & VEGF are central to angiogenesis Metastasis In a study on IL-1 and melanoma cells: IL-1 increased VLA-4 on melanoma cells IL-1 increased VCAM-1 in lungs IL-1Ra REDUCED metastasis in liver IL-1 plays a causal role in metastasis IL1 puts glueing molecules(VLA, ICAM,..) on the tumor AND on the site where the metastasis will come. Limitations of our model: 1). It is based on corroborative evidence => Test directly HH-IL-1-Cancer progression
Hypothesis IL-1 may mediate the epidemiological relationship between HH and cancer progression link between the psychological factors and the biological effects. IL1: lymphocyte proliferation, participates in many 'good' processes. If IL1 is blocked in the brain, mice do not develop helplessness! If put in a new situation with controllable stress: The mice who could escape the shock will learn the fastest The one's with learned helplessness just sit at the side. They don't try to stop it, they believe they can't. When they are given a IL1 blocker, they started to behave as if they came from the IS group could be entirely reversed! What does brain IL-1 do to cancer? Animals were injected with a peripheral tumour: Half were given IL-1 in the brain, half placebo Brain-IL-1 led to more metastases in the lungs than placebo. DUS: more IL1: more metastasis, aside from more HH! This was blocked by a beta-blocker, Nadolol Is helplessness associated with peripheral IL-1? A few studies showed that uncontrollable stress caused elevated levels of peripheral IL-1. More than other cytokines, IL-1 responds to this type of stress! If it causes more metastasis, it could be an important factor!! Is IL-1 associated with cancer-promoting events? Angiogenesis IL-1 plays a role in increasing IL-8 and VEGF Helplessness was positively correlated with VEGF in ovarian-cancer patients IL-8 & VEGF are central to angiogenesis Metastasis In a study on IL-1 and melanoma cells: IL-1 increased VLA-4 on melanoma cells IL-1 increased VCAM-1 in lungs IL-1Ra REDUCED metastasis in liver IL-1 plays a causal role in metastasis IL1 puts glueing molecules(VLA, ICAM,..) on the tumor AND on the site where the metastasis will come. Limitations of our model: 1). It is based on corroborative evidence => Test directly HH-IL-1-Cancer progression