Increased interleukin-2 production in response to human type I collagen stimulation in patients with systemic sclerosis.

Peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) produced increased amounts of interleukin-2 (IL-2), in a dose-dependent manner, in response to stimulation with human type I collagen, whereas PBMC from normal subjects did not. At a dose of 50 micrograms human type I collagen/10(6) PBMC, PBMC from SSc patients (n = 17) produced 8 times as much IL-2 as did PBMC from 16 normal subjects (P less than 0.005) and 3 times as much as did PBMC from a group of 13 rheumatoid arthritis patients (P less than 0.05). In contrast, IL-2 production by PBMC after nonspecific stimulation with the mitogen, phytohemagglutinin, did not differ among the SSc, rheumatoid arthritis, and normal control groups. Cell depletion experiments indicated that the IL-2-producing cells in SSc patients are CD4+. Thus, SSc patients have CD4 cells that are specifically sensitized to human type I collagen and can produce increased levels of IL-2. Measurement of IL-2 production stimulated by human type I collagen may be useful in evaluating disease activity, and further investigation of this process may contribute to the delineation of the pathogenesis of SSc.

An experimental model of carotid artery occlusive disease.

To develop an animal model for acute carotid artery occlusion suitable for studying the retinal sequelae of this disease, we performed bilateral and unilateral common carotid artery ligations on mature pigmented rats. Bilateral ligation consistently resulted in a characteristic pathologic retinal appearance, paralleling the retinopathy of carotid artery occlusive disease in humans, demonstrated by fundus photography and fluorescein angiography. Any abnormalities found in the rats with unilateral ligations were inconsistent and less severe, although fluorescein angiography proved to be more sensitive than ophthalmoscopy for detecting these subtle changes. Pepsin-trypsin retinal digests disclosed extensive disruption of the microvasculature in the eyes of bilaterally ligated animals. This model should prove to be useful in examining the reversibility of the ocular findings as well as evaluating central nervous system abnormalities after carotid artery occlusion.

Experimental carotid occlusion: funduscopic and fluorescein angiographic findings.

A characteristic fundus picture was consistently produced following acute bilateral common carotid artery ligation in mature rats, reminiscent of human carotid occlusive disease. Two days after ligation it consisted of dilatation and tortuosity of retinal veins, blurring and swelling of the optic disc, retinal whitening primarily along the venous distribution, and straightening of retinal arteries. Fluorescein angiography showed hyperfluorescence of the disc, delay in the rate of retinal arterial and venous filling, venous dilatation, disc oedema, disruption of the retinal capillary bed pattern, and late peripapillary staining/leakage. This pattern was not seen in rats which underwent acute unilateral ligation, although some mild changes were seen on fluorescein angiography. The vascular alterations seemed to regress spontaneously within one week. A peripapillary 'halo' and a granular-appearing nerve fibre layer developed later, exclusively in bilaterally ligated animals.