Validation of the Candida albicans delayed-type hypersensitivity (DTH) model in the female B₆C₃F₁ mouse for use in immunotoxicological investigations

Figures & data

Figure 1.  Effects of AZA exposure on the DTH response to C. albicans. Mice were administered either vehicle (0.5% methylcellulose) or AZA PO daily for 28 days. Mice were sensitized on Day 21 with C. albicans. The right footpad of each mouse was pre-measured and challenged with chitosan antigen on Day 29, with post-measurement occurring 24 [± 2] h after challenge. The background footpad swelling was determined in a group of mice that were challenged but not sensitized (challenge only). The data are expressed as footpad swelling (mm × 100). Values represent the mean (± SE) of two combined studies, each containing 7–8 animals per group. Vehicle control means between studies were not statistically significantly different (57.1 [± 10.0] vs 53.4 [± 11.7] mm × 100). ** p < 0.01.

Figure 2.  Effects of CPS exposure on the DTH response to C. albicans. Mice were administered either vehicle (PBS) or CPS IP daily for 28 days. Mice were sensitized on Day 21 with C. albicans. The right footpad of each mouse was pre-measured and challenged with chitosan antigen on Day 29, with post-measurement occurring 24 [± 2] h after challenge. The background footpad swelling was determined in a group of mice that were challenged but not sensitized (challenge only). The data are expressed as footpad swelling (mm × 100). Values represent the mean (± SE) of two combined studies, each containing 7–8 animals per group. Vehicle control means between studies were not statistically significantly different (78.4 [± 9.2] vs 62.9 [± 7.1] mm × 100). * p < 0.05; ** p < 0.01.

Figure 3.  Effects of CSA exposure on the DTH response to C. albicans. Mice were administered either vehicle (corn oil) or CSA PO daily for 28 days. Mice were sensitized on Day 21 with C. albicans. The right footpad of each mouse was pre-measured and challenged with chitosan antigen on Day 29, with post-measurement occurring 24 [± 2] h after challenge. The background footpad swelling was determined in a group of mice that were challenged but not sensitized (challenge only). The data are expressed as footpad swelling (mm × 100). Values represent the mean (± SE) of two combined studies, each containing 7–8 animals per group. Vehicle control means between studies were not statistically significantly different (78.4 [± 8.0] vs 65.1 [± 10.4] mm × 100). ** p < 0.01.

Figure 4.  Effects of DEX exposure on the DTH response to C. albicans. Mice were administered either vehicle (0.5% methylcellulose) or DEX PO daily for 28 days. Mice were sensitized on Day 21 with C. albicans. The right footpad of each mouse was pre-measured and challenged with chitosan antigen on Day 29, with post-measurement occurring 24 [± 2] h after challenge. The background footpad swelling was determined in a group of mice that were challenged but not sensitized (challenge only). The data are expressed as footpad swelling (mm × 100). Values represent the mean (± SE) of two combined studies, each containing 7–8 animals per group. Vehicle control means between studies were not statistically significantly different (71.0 [± 7.6] vs 60.3 [± 7.9] mm × 100. ** p < 0.01.

Figure 5.  Lack of effect of B[e]P exposure on the DTH response to C. albicans. Mice were administered either vehicle (corn oil) or B[e]P SC daily for 28 days. Positive control mice were administered (IP) 50 mg/kg CPS on Days 25–28. Mice were sensitized on Day 21 with C. albicans. The right footpad of each mouse was pre-measured and challenged with chitosan antigen on Day 29, with post-measurement occurring 24 [± 2] h after challenge. The back-ground footpad swelling was determined in a group of mice that were challenged but not sensitized (challenge only). The data are expressed as footpad swelling (mm × 100). Values represent the mean (± SE) from eight animals per group.

Table l.  Comparison of the C. albicans DTH model with ex vivo studies by Lebrec et al. (1994).

	CPS (mg/kg/day)		DEX (mg/k g/day)		AZA (mg/kg/day)		CSA (mg/kg/day)
	Effect Level	NOEL	Effect Level	NOEL	Effect Level	NOEL	Effect Level	NOEL
C. albicans DTH	≥10	5	≥0.3	0.03	≥20	10	≥3	1
			(intermittant effects at 0.1)
Doses Utilized	3, 5, 10, 20, 30		0.03, 0.1, 0.3, 0.5, 1		3, 5, 10, 20, 30		0.3, 1, 3, 10, 30
Ex vivo Endpoints
Lebrec et al. (1994)
Con A	Not Conducted		0.5	0.1	NE	20	50	25
PHA	Not Conducted		0.5	0.1	NE	20	≥12.5	ND
Anti-CD3	Not Conducted		0.5	0.1	NE	20	50	25
MLR	Not Conducted		NE	0.5	NE	20	≥25	12.5
CTL	Not Conducted		0.5^a	0.1	NE	20	≥25	125
Doses Utilized	Not Conducted		0.02, 0.1, 0.5		0.8, 4, 20		12.5, 25, 50

^aStudy showed an effect in this parameter at a lower dose, but it was not observed at a higher dose. NE = NoEffect, ND = Not Determined.

Lebrec H., Blot C., Pequet S., Roger R., Bohuon C., and Pallardy M. 1994. Immunotoxicological investigation using pharmaceutical drugs: In vivo evaluation of immune effects. Fundam. Appl. Toxicol. 23:159–168.

 PubMedGoogle Scholar