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More than 1.3 billion people smoke tobacco worldwide, and each year, about 30 million people take up smoking, with the rate of smoking increasing at greater than 3% annually in developing countries. The World Health Organization estimates that by 2030 10 million deaths per year worldwide will be directly attributable to tobacco consumption. The Centers for Disease Control and Prevention estimates that in the United States the annual cost of tobacco consumption is in excess of $167 billion due to lost productivity and smoking-related health-care costs. While an association between tobacco smoking and severity and incidence of chronic disease is well established, it has only recently been appreciated that a gender disparity exists in this effect. Some diseases are more severe in women who smoke, and this is of particular concern since recent reports describe an alarming increase in the rate of smoking among women worldwide. Furthermore, in the United States smoking rates among adolescents is now the same in girls and boys, and women have a lower smoking cessation rate than men. Since women are at escalating risk of various diseases affected by tobacco, there is an urgent need for scientific studies in this neglected field of research.
There are several diseases affected by tobacco that differentially affect men and women, including inflammatory diseases such as chronic obstructive pulmonary disease, psoriasis, Crohn's disease and rheumatoid arthritis. Sex hormones, such as estrogen, influence the effect of smoking on some of these diseases; for example, smoking worsens rheumatoid arthritis in post-menopausal women, while in pre-menopausal women smoking may protect against rheumatoid arthritis.
Smoking, and in particular, it's main pharmacologically active ingredient, nicotine, affects many aspects of inflammation, such as the functioning of immune cells and anti-inflammatory effects of stress mediated by the release of adrenaline from the adrenal medulla.
We propose to study, in rats, how nicotine affects two key components of inflammation: the ability of immune cells (white blood cells) to fight bacterial infections (move towards, engulf and destroy bacteria) and the 'leakiness' of blood vessels (plasma extravasation, which accounts for tissue swelling in inflammation). We will determine the effects of nicotine on these components of inflammation and examine sex differences in the response to nicotine, and the role of sex hormones.
We have previously shown that there is a sex difference in the role of the adrenal medulla in influencing inflammation. Since one of nicotine's main effects is to act on the adrenal medulla to release adrenaline, we will evaluate the contribution of the adrenal medulla to the sex differences in the effects of nicotine on inflammation. Finally, since there are similarities in smoking withdrawal symptoms and symptoms that occur during inflammation (i.e. sickness symptoms), it has been suggested that symptoms of nicotine abstinence are, at least in part, inflammatory in nature. Since women have a lower smoking cessation rate than men, possibly because of worse withdrawal symptoms, we will evaluate the effect of nicotine withdrawal on sex differences in inflammation.
These studies will give us a better understanding of the basic mechanisms underlying sex differences in the effects of smoking on inflammatory diseases and also, possibly, smoking cessation. |
