Mild Acute Inflammation Research Articles

Granulomatous enterocolitis induced in rats by purified bacterial cell wall fragments

This study was designed to determine if poorly biodegradable bacterial cell wall components can produce chronic intestinal inflammation. A sterile aqueous suspension of sonically disrupted group A or group D streptococcal cell wall fragments was injected intramurally into the small intestine and cecum of 100 rats. Gross findings in rats killed at intervals of 1 day to 6 mo included intestinal thickening, adhesions, and mesenteric contraction. Acute histologic inflammation subsided by 2 wk, but chronic granulomatous inflammation persisted for 6 mo in the rats injected with group A streptococcal cell wall fragments and 3 mo in the rats injected with group D streptococcal cell wall fragments. Ninety-six control rats identically injected with human serum albumin or phosphate-buffered saline demonstrated mild acute inflammation that resolved, with only 1 rat having chronic intestinal inflammation. Granulomas in the intestine, mesentery, and mesenteric lymph nodes developed in 46% of the rats injected with group A fragments and 45% of the rats injected with group D streptococcal cell wall fragments, compared with 20% of the controls injected with albumin and 4% of the controls injected with phosphate-buffered saline. Group A streptococcal antigen was detected by immunofluorescence at the site of inflammation for 4 mo, and possible reactivation of acute inflammation was seen up to 6 mo after injection. We conclude that bacterial cell wall fragments are capable of producing chronic granulomatous inflammation in the intestinal wall if present in appropriate particle size and concentration. We speculate that cell walls from the enteric microflora may leak across a permeable mucosa in chronic inflammatory bowel disease to initiate and sustain local and systemic inflammation.

Dysentery caused by Escherichia coli (S102-9) in calves: natural and experimental disease.

A dysentery syndrome was recognized among the Institute's calves at 18 to 21 days of age. It was reproduced experimentally in gnotobiotic calves with an atypical Escherichia coli (S102-9) isolated from the affected calves. In both natural and experimental disease the calves passed copious bright red blood in the feces and developed diarrhea. Walls of the colon and rectum were thickened, and the mucosa was reddened and covered by an exudate that contained mucus and blood clots. Bacteria were seen closely adherent to the luminal surfaces of enterocytes, often in cup-shaped depressions or on cytoplasmic pedestals. Microvilli were distorted, disorientated or absent. There was exfoliation of infected enterocytes and a mild acute inflammation of the underlying lamina. In two of five calves with natural disease, the adherent bacteria did not stain by the immunoperoxidase method with antisera raised against E. coli (S102-9). This indicated that there was possibly more than one bacterial cause of the syndrome. Lesions in experimentally infected calves were indistinguishable from those produced by some E. coli which are enteropathogenic for man, rabbits, and pigs.

Variables affecting local immune response in ileal loops: role of immunization schedule, bacterial flora, and postsurgical inflammation.

Several variables inherent in chronically isolated ileal (Thiry-Vella) loops in rabbits were studied for their effect on the local immune response of the intestine to live, locally invasive bacteria (Shigella X16). A much more vigorous local immunoglobulin A response to Shigella X16 was elicited when rabbits were immunized in their Thiry-Vella loops shortly after surgical creation of the loop than if a week were allowed to pass before they were immunized. Three major differences existed in Thiry-Vella loops on the day after surgery and a week later: (i) their microbial flora, (ii) nonspecific acute inflammation due to the surgery itself, and (iii) the histological appearance of the intestine. On day 1 after surgical creation of the Thiry-Vella loop, there were few bacteria in the loop, and the histology was that of normal small bowel except for mild acute inflammation due to the surgery. By day 6 after surgery, all loops contained large numbers of Pseudomonas aeruginosa and other aerobes, an atrophy of intestinal epithelium occurred, and the acute inflammation due to surgical trauma had subsided. By artificially colonizing Thiry-Vella loops with 10(8) or 10(10) live P. aeruginosa on the day of surgery, we found that the presence of these bacteria alone did not greatly diminish local immune responses to live Shigella. Furthermore, when the acute inflammation due to surgical trauma was recreated in loops 6 days old, no enhancement of the immune response was seen as compared to nontraumatized 6-day-old Thiry-Vella loops. The difference between immunization soon after surgery and a week later related to changes that occur in the loop itself with increased isolation. Finally, multiple immunizations of Thiry-Vella loops resulted in a more vigorous local immunoglobulin A response than a single immunization. These studies demonstrated that Thiry-Vella loop models can be useful in studying the kinetics of local immune responses by the intestine only if careful attention is paid to key variables inherent in the Thiry-Vella loop models themselves.

STUDIES ON DECREASING THE REACTION OF NORMAL SKIN TO DESTRUCTIVE DOSES OF X-RAYS BY PHARMACOLOGICAL MEANS AND ON THE MECHANISM INVOLVED

When a fixed area of the ears of rabbits is subjected to the action of a standard destructive dose of x-rays (30 skin units) the type of reaction resulting depends upon the previous treatment of the rabbit. (1) In normal rabbits a mild acute inflammation develops in the x-rayed area which leads at once to a perforating gangrene within an average of 15 days. (2) If rabbits are x-rayed and about 2 weeks later injected with horse serum for the first time, a mild acute inflammation appears which heals for a time; then a second, subacute inflammation sets in which leads to a perforating gangrene. The average time of the process from the first inflammation to gangrene is 32 days. (3) If rabbits are sensitized with horse serum and 10 days later are exposed locally to the standard dose of x-rays, the ensuing ear reaction is either similar to the second reaction described above, except that it may last up to 110 days, or the first inflammation leads to a healing which may be apparently permanent (340 + days). (4) If rabbits are first sensitized with horse serum, exposed locally to the standard dose of x-rays 10 days later, and 13 days after the x-ray treatment reinjected with horse serum, the reaction of the x-rayed area of the ears is in general similar to the second reaction described above (inflammation-healing-inflammation-gangrene). The average time of the whole process is about 42 days. On the basis of the general hypothesis that an anaphylactic reaction is initiated in the body when the specific antibody meets its antigen, and that both antibody and antigen are rendered more or less functionally inert by their interaction, the following inferences may be drawn from our experimental results. (1) The protection from the effects of a standard destructive dose of x-rays which a previous sensitization confers, is referable to the presence of anaphylactic antibodies in the x-rayed area. (2) This protection is largely due to the anaphylactic antibodies which are anchored in the x-rayed area, and not to those which are free in the circulation. (3) An anaphylactic reaction renders the anchored anaphylactic antibodies largely impotent as protective factors against the standard destructive x-ray dose, even though sensitization preceded exposure to the x-rays. (4) An area treated with the standard destructive dose of x-rays is unable to produce or to anchor a sufficient amount of anaphylactic antibodies for protection from necrosis, when the x-ray treatment precedes the sensitization, or when the locally anchored anaphylactic antibodies are rendered functionally inactive by a general anaphylactic reaction. It is possible that the procedure of increasing the resistance of the skin to a destructive dose of x-rays by means of a previous sensitization with protein may be applicable in the treatment of certain types of inoperable disease, when it is important to use massive doses of x-rays. Animals which have been sensitized, or sensitized and reinjected with any undenatured alien protein, should not be reemployed as normal controls in any investigation unless trial has shown that these proteinized animals react quantitatively and qualitatively like normal animals. The presence of an abnormal reactor in a group of supposedly normal animals may be an indication of a previous proteinization.