Int. Archs Allergy appl. Immun. 52: 425-427 (1976)
Carrageenan and Dextran in Rats R. E. Anderson, P. J. Warne and G. B. West Department of Applied Biology, North East London Polytechnic, London
Abstract. Carrageenan injected subcutaneously into one hindpaw of the rat produces an anaphylactoid reaction which prevents the same paw responding to a second dose 14 days later but does not alter the response to dextran. However, dextran does not modify the response of the hindpaw to a subsequent dose of either dextran or carrageenan 14 days later. When using these models of inflammation for testing the anti-inflammatory activity of drugs, valuable extra information may be gained by adopting the cross-over technique and using both paws of each animal.
Received: June 17, 1976.
correspondingly with dextran, carrageenan and then dextran. Control responses were consistent using this procedure although in jury at one site has been shown often to in hibit the inflammatory response at another part of the body [Thomas and West, 1973], possibly through the production of a natural anti-inflammatory agent or through the re lease of catecholamines or corticosteroids. The problem needed further study to deter mine the limitations of the proposed proce dure of using the same paw repeatedly for the same stimulus. Groups of 6 Wistar rats (120-160 g) from the Tuck Colony were injected into the right hind paw with either 1 mg carrageenan (Viscarin, Marine Colloids Inc.) or 1 mg dextran (Dextraven, molecular weight Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 1:38:44 PM
Both carrageenan and dextran anaphy lactoid reactions in rat paws are useful ex perimental models of inflammation for the testing of anti-inflammatory activity of new drugs. Possibly valuable extra information can be gained when the two injurious stimu li are administered at the same time, one into each of the paws of the same animal. This type of procedure has already been tested [Harper and West, 1977] when a study of the effects of insulin and alloxan on these two responses in the same animal was made at different times. These authors used the cross-over technique, in which one hind paw first received carrageenan, was then given dextran 7 days later, and after a fur ther 14 days was injected again with carra geenan. The other hand paw was injected
Time, h
Time, h
Fig. 1. Mean percentage increases (+ SEM) in paw volumes of the same groups of 10 rats pro duced by carrageenan (1 mg) into the left hind paw (A) and dextran (1 mg) into the right hind paw (B) at different times (in hours) on day 1 (O) and again on day 14 (# ). Also shown (X) are the carrageenan responses 14 days after dextran into the right paw (but recorded in A) and the dextran response 14 days after carrageenan into the left paw (but recorded in B).
110,000). Each dose was administered in 0.1 ml 0.9°/o NaCl solution and the increases in paw volumes were recorded on a differ ential volume meter every 30 min for 5 h. Increases of about 70% were recorded in each case (fig. 1), the peak for carrageenan being 4 h and that for dextran 1 h. When tested 7 days later with the same stimuli in the same paws, the action of car rageenan was suppressed whereas that of dextran was unaffected (fig. 1). In other groups of rats, the action of carrageenan was similarly suppressed when the second carrageenan injection was made 14 days af ter the first. After 21 days, however, recov ery was apparent. When dextran was inject ed into a paw which had received carra geenan previously, the dextran response was unaltered, and, similarly, when carrageenan
was injected into a paw which had received dextran, the carrageenan response was unal tered. In all of these experiments, the vol ume of a paw after a single injection of car rageenan 7-14 days previously was some 20% more than that of the other paw of the same animal. Thus one dose of carrageenan produces a long-lasting swelling of the hind paw which interferes with the subsequent carrageenan response but not that to dex tran. Finally, groups of rats were given carra geenan into the left hind paw and at the same time dextran into the right paw. The increases in paw volume were again about 70%, showing that one response does not alter the other in the same animal. When tested 7 days later with the same stimuli in the same paws, the carrageenan response was suppressed although that to dextran was unchanged. Similar results were obtained in other groups of rats tested 14 days after the first injections. However, in other animals the carrageenan response was unaffected when it was injected into the right hind paw only 7 days after the dextran response. It is concluded that the dextran response in the hind paw of the rat is short-lived and the paw rapidly returns to its initial condi tion so that other stimuli can be adminis tered 7 days later and produce consistent control responses. In the same animal, the carrageenan response is prolonged and even at 14 days the paw is swollen and the subse quent carrageenan response is suppressed although that to dextran remains un changed. The results suggest that both hindpaws of the rat can be used at the same time on several occasions for testing anti-inflam matory agents, provided the stimuli of car rageenan and dextran are applied at least 1 month after the first injections.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 1:38:44 PM
Anderson/Warne/West
426
References Harper, D. and West, G. B.: Anaphylactoid reac tions in rats and the blood sugar level. Int. Archs Allergy appl. Immun. 52: 407-411 (1977). Thomas, G. and West, G. B.: The action of an ti-inflammatory drugs in two models of in-
427
flammation. J. Pharm. Pharmac. 25: 753-754 (1973).
Correspondence to: Dr. G. B. West, Department of Applied Biology, North East London Polytech nic, Romford Road, London, E.15 (England)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 1:38:44 PM
Carrageenan and Dextran in Rats
Carrageenan and Dextran in Rats R. E. Anderson, P. J. Warne and G. B. West Department of Applied Biology, North East London Polytechnic, London
Abstract. Carrageenan injected subcutaneously into one hindpaw of the rat produces an anaphylactoid reaction which prevents the same paw responding to a second dose 14 days later but does not alter the response to dextran. However, dextran does not modify the response of the hindpaw to a subsequent dose of either dextran or carrageenan 14 days later. When using these models of inflammation for testing the anti-inflammatory activity of drugs, valuable extra information may be gained by adopting the cross-over technique and using both paws of each animal.
Received: June 17, 1976.
correspondingly with dextran, carrageenan and then dextran. Control responses were consistent using this procedure although in jury at one site has been shown often to in hibit the inflammatory response at another part of the body [Thomas and West, 1973], possibly through the production of a natural anti-inflammatory agent or through the re lease of catecholamines or corticosteroids. The problem needed further study to deter mine the limitations of the proposed proce dure of using the same paw repeatedly for the same stimulus. Groups of 6 Wistar rats (120-160 g) from the Tuck Colony were injected into the right hind paw with either 1 mg carrageenan (Viscarin, Marine Colloids Inc.) or 1 mg dextran (Dextraven, molecular weight Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 1:38:44 PM
Both carrageenan and dextran anaphy lactoid reactions in rat paws are useful ex perimental models of inflammation for the testing of anti-inflammatory activity of new drugs. Possibly valuable extra information can be gained when the two injurious stimu li are administered at the same time, one into each of the paws of the same animal. This type of procedure has already been tested [Harper and West, 1977] when a study of the effects of insulin and alloxan on these two responses in the same animal was made at different times. These authors used the cross-over technique, in which one hind paw first received carrageenan, was then given dextran 7 days later, and after a fur ther 14 days was injected again with carra geenan. The other hand paw was injected
Time, h
Time, h
Fig. 1. Mean percentage increases (+ SEM) in paw volumes of the same groups of 10 rats pro duced by carrageenan (1 mg) into the left hind paw (A) and dextran (1 mg) into the right hind paw (B) at different times (in hours) on day 1 (O) and again on day 14 (# ). Also shown (X) are the carrageenan responses 14 days after dextran into the right paw (but recorded in A) and the dextran response 14 days after carrageenan into the left paw (but recorded in B).
110,000). Each dose was administered in 0.1 ml 0.9°/o NaCl solution and the increases in paw volumes were recorded on a differ ential volume meter every 30 min for 5 h. Increases of about 70% were recorded in each case (fig. 1), the peak for carrageenan being 4 h and that for dextran 1 h. When tested 7 days later with the same stimuli in the same paws, the action of car rageenan was suppressed whereas that of dextran was unaffected (fig. 1). In other groups of rats, the action of carrageenan was similarly suppressed when the second carrageenan injection was made 14 days af ter the first. After 21 days, however, recov ery was apparent. When dextran was inject ed into a paw which had received carra geenan previously, the dextran response was unaltered, and, similarly, when carrageenan
was injected into a paw which had received dextran, the carrageenan response was unal tered. In all of these experiments, the vol ume of a paw after a single injection of car rageenan 7-14 days previously was some 20% more than that of the other paw of the same animal. Thus one dose of carrageenan produces a long-lasting swelling of the hind paw which interferes with the subsequent carrageenan response but not that to dex tran. Finally, groups of rats were given carra geenan into the left hind paw and at the same time dextran into the right paw. The increases in paw volume were again about 70%, showing that one response does not alter the other in the same animal. When tested 7 days later with the same stimuli in the same paws, the carrageenan response was suppressed although that to dextran was unchanged. Similar results were obtained in other groups of rats tested 14 days after the first injections. However, in other animals the carrageenan response was unaffected when it was injected into the right hind paw only 7 days after the dextran response. It is concluded that the dextran response in the hind paw of the rat is short-lived and the paw rapidly returns to its initial condi tion so that other stimuli can be adminis tered 7 days later and produce consistent control responses. In the same animal, the carrageenan response is prolonged and even at 14 days the paw is swollen and the subse quent carrageenan response is suppressed although that to dextran remains un changed. The results suggest that both hindpaws of the rat can be used at the same time on several occasions for testing anti-inflam matory agents, provided the stimuli of car rageenan and dextran are applied at least 1 month after the first injections.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 1:38:44 PM
Anderson/Warne/West
426
References Harper, D. and West, G. B.: Anaphylactoid reac tions in rats and the blood sugar level. Int. Archs Allergy appl. Immun. 52: 407-411 (1977). Thomas, G. and West, G. B.: The action of an ti-inflammatory drugs in two models of in-
427
flammation. J. Pharm. Pharmac. 25: 753-754 (1973).
Correspondence to: Dr. G. B. West, Department of Applied Biology, North East London Polytech nic, Romford Road, London, E.15 (England)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/5/2018 1:38:44 PM
Carrageenan and Dextran in Rats
