Enhanced humoral antibody production and delayed type hypersensitivity response in mice by Lactobacillus casei.

Antibody titers against Pseudomonas aeruginosa in sera from mice were markedly elevated by pre-injection of Lactobacillus casei. The number of plaque-forming cells against sheep red blood cells ( SRBC) in the spleen of mice pretreated with L. casei was highter than those in the controls. L. casei also enhanced the delayed type hypersensitivity response against SRBC in mice. Therefore, it was revealed that L. casei possesses the actions of humoral and cellular immunopotentiation. Bacterial nonspecific stimulators of host defense (immunostimulators) such as Bacillus Calmette-Guerin (BCG), Propionibacterium acnes (Corynebacterium parvum), attenuated Streptococcus pyogenes (OK-423) and cellular components of these microorganisms activate cell-populations of the reticuloendotherial system. One major site of action of these stimulants is the macrophage2' 4, 9>. These agents also stimulate the lymphocytes, granulopoiesis8>, the complement system11' 13> and the production of interferon12> and humoral antibodies1,16>. Kato et al. 10> reported the marked antitumor activity of Lactobacillus casei YIT -9018 (LC 9018) against allogeneic and syngeneic tumors in mice. We also recently found that the pretreatment of mice with L. casei YIT-0003 causes a marked increase in resistance to challenge with Listeria monocytogcnes and Pseudomonas aeruginosa14' 15>. It is also known that L. plantarum and L. casei possess adjuvant activities3' 7>. As little is known of the humoral antibody producing effects of L. casei, we studied the effects of L. casei on the production of antibody and the antibody producing cells against the heat-killed P. aeruginosa and sheep red blood cells ( SRBC) in mice. L. casei YIT-0003 cells grown in Rogosa's medium6> at 37°C for 18 hr were washed and suspended in saline. Each of five-week-old female ddY mice was given intravenously (iv) a 0. 2 ml of a 5 x 108 /ml saline suspension of live or heat-killed (at 80°C forl 30 min) L. casei three times at 24 hr interv~ls. Control mice were given injections of 0. 2 ml of saline under the same conditions. Forty-eight hr after the last injection, these mice were immunized subcutaneously (sc) with a 0. 1 ml of 3x109 /ml saline suspension of heat-killed (at 100°C for 60 min) P. aeruginosa PAO 3047 three times at 24 hr intervals. After the third immunization, blood was taken from the heart of these animals at various time intervals. The serum was separated by centrifugation and stored at 20° C until use. Sero-agglutination tests were carried out with a microplate. The serum (25 μl) was serially diluted 2-fold with saline and mixed with an equal volume of heat-killed (at 120°C for 90 min) P. aeruginosa (1. 5x109 /ml). The reaction mixture was incubated at 37° C for 2 hr and kept at 4° C for 24 hr. As shown in Fig. 1, the mean values of antibody titers 5 and 8 days after P. aeruginosa injection in the L. casei-treated group were *> lilfi •· fti:lfilml§, #ffiJll&-1:!?., 1\Jll ~m:. ~riaJrailJJ, mtilllliRJ: ~L~~M(J)"'tJ;A.~c:tovtQ:btf*ii:~:toJ:lf'JI!~ ~~t$::fil:Bz:Jit(J):It]5~