Tumor necrosis factor in CHF: a double facet cytokine

Time for primary review 40 days. Tumor necrosis factor (TNF) gained its popularity in the world of biology and medicine in a weird way. In 1985, Old in New York City discovered the presence of a protein in blood after lipopolysaccharide (LPS) injection, which is able to induce necrosis of some mouse tumors 1. He called it ‘tumor necrosis factor’ , a term actually coined in the 1970s. At the same time and, virtually, on the other side of the street, Beutler and Cerami, working at what may appear as an unsurmountable biological distance, discovered that the intriguing state of cachexia is associated with the presence of a protein called ‘cachectin’ in the serum 2. Its purification made them realize that ‘cachectin’ is an essential mediator of the state of LPS-induced shock and that it is the same molecule of ‘tumor necrosis factor’ 2. It took some years for these three parents to recognize that their child, whatever called, was unusually gifted. They could not foresee that TNF turned out to be a prodigy molecule eliciting the publication of many papers per day 3. Two names are not enough to describe TNF, as we now distinguish TNF-α from its twin, TNF-β or ‘lymphotoxin’ (LT), a lymphokine which has only a 30% homology with TNF-α but which binds to the same receptors 4. Despite similarities, these two proteins do not always transduce identical signals; they have distinct cellular sources and regulation mechanisms. Strangely enough, and without any particular reason, there are many more studies on TNF-α than TNF-β. Herein the current knowledge on the involvement of TNF-α in congestive heart failure (CHF) is reviewed. For the sake of simplicity, we will refer to TNF-α as TNF. TNF is a trimeric 17-KDa polypeptide mainly produced by monocytes …