Abstract. Interleukin-I (IL-1) is synthesized by and released from macrophages in response to a variety of stimuli and appears to play an essential role in virtually all inflammatory conditions. In tissues of mesenchymal origin (e.g., cartilage, muscle, bone, and soft connective tissue) ILl induces changes characteristic of both destructive as well as reparative phenomena. Previous studies with natural IL-1 of varying degrees of purity have suggested that it is capable of modulating a number of biological activities of fibroblasts. We have compared the effects of purified human recombinant (hr) IL-la and !~ on several fibroblast functions. The parameters studied include cell proliferation, chemotaxis, and production of collagen, collagenase, tissue inhibitor of metalloproteinase (TIMP), and prostaglandin (PG) E2. We observed that hrlL-ls stimulate the synthesis and accumulation of type I procollagen chains. Intracellular degradation of collagen is not altered by the hrlL-ls. Both IL-ls were observed to increase the steady-state levels of pro al(I) and pro a2(I) mRNAs, indicating that they exert control of type I procollagen gene expression at the pretranslational level. We found that both hrlL-la and 13 stimulate synthesis of TIMP, collagenase, PGE2, and growth of fibroblasts in vitro but are not chemotactic for fibroblasts. Although hrlL-la and 13 both are able to stimulate production of PGE2 by fibroblasts, inhibition of prostaglandin synthesis by indomethacin has no measurable effect on the ability of the IL-ls to stimulate cell growth or production of collagen and collagenase. Each of the IL-ls stimulated proliferation and collagen production by fibroblasts to a similar degree, however hrlL-113 was found to be less potent than hrlL-1 a in stimulating PGE2 production. These observations support the notion that IL-l~t and 13 may both modulate the degradation of collagen at sites of tissue injury by virtue of their ability to stimulate collagenase and PGE2 production by fibroblasts. Furthermore, IL-la and 13 might also direct reparative functions of fibroblasts by stimulating their proliferation and synthesis of collagen and TIMP.

Laser scar revision was studied to measure the effects of targeting extracellular matrix protein versus tissue water on scar revision. We compared the free electron laser used at 7.7 microm (the amide III protein absorption band) to the carbon dioxide (CO2) laser and dermabrasion.Nude mice (n = 40) that had rejected skin grafts on their dorsal surface and developed mature scars were used as a model for scar revision. One-half of each scar was revised with either the free electron laser at 7.7 microm (32 to 38 mJ, nonoverlapping pulses delivered with a computerized adjustable pattern generator at 30 Hz, and two to three passes), a 100-microsec CO2 resurfacing laser (500 mJ, 5.0 Hz, and two to five passes), or dermabrasion. The untreated portion of each scar served as an internal control. Evaluation was by measurement of the clinical size of the scar using photography with quantitative computer image analysis to compare the data and histology to evaluate the quality and depth of the scars. The free electron laser at 7.7 microm was significantly better than the CO2 laser and dermabrasion for scar size reduction (p < 0.046 and p < 0.018). The CO2 laser and a highly skilled dermabrader were not statistically significantly different (p < 0.44). The result seen with less skilled dermabraders was significantly worse than all other methods (p < 0.009). The free electron laser at 7.7 microm, which is preferentially absorbed by the proteins of the extracellular matrix, provided better scar reduction than the CO2 resurfacing laser and dermabrasion. Dermabrasion by a skilled operator resulted in improvement similar to the results obtained with the CO2 resurfacing laser, but less skilled operators had significantly poorer results.