Which of the following statements regarding fibroblasts and their function in wound healing are true?

a. IL-1 has both inhibitory and promotional effects on fibroblast growth

d. In human clinical trials, EGF (epithelial growth factor) has been demonstrated to accelerate epidermal regeneration in cutaneous wounds

IL-1 appears to be important in the process of normal wound repair. IL-1 has been shown to stimulate skin fibroblast and keratinocyte growth, as well as fibroblast collagen synthesis and keratinocyte chemotaxis. IL-1 also promotes increased transcription of the matrix degradative enzymes collagenase and stromelysin. These are important and potent tissue degrading proteinases. Other studies have demonstrated that IL-1 inhibits fibroblast growth and matrix synthesis, and stimulates collagenase production. These actions are at least partly due to the ability of IL-1 to upregulate prostaglandin E2 production which results in the down regulation of matrix synthesis. IL-1 has both promoting and inhibiting effects on fibroblast collagen synthesis, therefore, the overall activity in this area is somewhat unclear in comparison to other welldefined fibroblast growth-promoting cytokines. TNFa inhibits fibroblast collagen synthesis, however it also has potent mitogenic effects. The mitogenic response correlates well with an increased stimulation of tyrosine phosphorylation. Both IL-1 and TNFa have similar effects upon bone. Both stimulate cartilage resorption, the release of proteoglycans from cartilage by limited proteolytic degradation, and both inhibit proteoglycan synthesis. Recent studies have also demonstrated that TNFa inhibits fracture healing in experimental animals. This is due to the inhibition of cartilage formation and new bone synthesis, and the inhibition of mesenchymal cell differentiation into chondroblasts. The family of epithelial growth factor (EGF)-like molecules induce mitogenesis and play a role in wound healing. In human clinical trials, EGF has been demonstrated to accelerate epidermal regeneration in cutaneous wounds. In vitro data show that recombinant EGF enhances keratinocyte migration. EGF is also a potent chemoattractant for granulation tissue fibroblasts.