Role of L-lysine HCl in adoptive immune therapy towards development of suitable tuberculosis vaccination.

L-Lysine HCI is being proposed to be a possible biocompatible adjuvant to enhance immune response by virtue of its probable non-specific bridging action and cellular proliferation properties. This proposal has been tried to be substantiated by designing an in vitro culture protocol, varying the concentration of L-lysine HCI and its further in vivo application. Splenic lymphocyte population has been extracted from mice and co-cultured with extracted mice macrophage population in presence of either Bacille Calmette Guerrin (BCG) or Hepatitis B surface antigen (HbsAg) and added L-lysine hydrochloride in culture media. Post incubation of these cultures, "taught" cell population has been adoptively transferred in naïve mice. These mice were then challenged by respective antigen dose, Change in Immune response with this challenge was noted. Antibody titre was followed in all the experiments as a measure of immune response. In adoptive immune transfer experiment of with HbsAg (AIT-HbsAg), similar to that with BCG (AIT-BCG), after the incubation period, antibody titre was higher in added lysine containing cultures in comparison with the control ones. Post transfer followed by antigen challenge, in AIT-BCG the expected augmentation in immune response was hardly visible. But in AIT-HbsAg, with the help of lysine booster, the animals responded better as far as the antibody titre is concerned.

Role of L-lysine HCl in immunopotentiation towards development of suitable tuberculosis vaccination.

L-Lysine HCl is being proposed to be a possible biocompatible adjuvant to enhance immune response by virtue of its probable non-specific bridging action and cellular proliferation properties. This proposal has been tried to be substantiated by carrying out experimentation where L-lysine HCl has been used as an adjuvant (various groups based on mode of application and frequency of booster dose were designed) in tuberculosis vaccination experiments with heat killed Mycobacterium tuberculosis (MTB) and Bacille Calmette Guerin (BCG). Antibody titre has been followed in all the experiments as a measure of immune response. Amongst the various groups designed, group 1A (L-lysine HCl was given at a separate site as that of the antigen; lysine booster was given to this group intermittently, i.e. lysine given on 0th, 7th, 14th, 21st days of immunization) came out as the stand-alone leader. This mode and frequency of application was then compared with a group which received a standard adjuvant, viz. alhydrogel. Results were obtained which showed the following order in terms of decreasing antibody titre: alhydrogel group > lysine group > control group. Considering the biocompatible nature of lysine in comparison with the reportedly hazardous nature of alum adjuvants, we propose L-lysine HCl as a probable adjuvant in vaccination.

Lysine: Is it worth more?

Lysine, an essential cationic amino acid, has a positively charged R group. The structure of lysine is given as (H(3)N(+)-)CH(-COO(-))-CH(2)-CH(2)-CH(2)-CH(2)-N(+)H(3).While the anabolic role(s) of the molecule has been in focus for quite a few decades now, its biological properties, e.g. role in cellular proliferation in vitro (both anchorage dependent and anchorage independent) and in vivo, its ability to induce strong inflammatory and immune responses - both humoral and cell mediated, its role in augmented healing of all types of wounds in animal models as well as in human subjects (both acute and chronic), as well as its role in inducing extensive angiogenic responses, have never received reasonable attention so far. In the current brief and indicative review (rather than exhaustive reviews of each area), we intend to bring these biological properties of the molecule to focus while discussing a few other interesting aspects - lysine as a food preservative as well as its possible role(s) in immune therapy. While the areas look extremely divergent, we propose a common denominator in the form of a possible molecular mechanism of action of the molecule in all these diverse situations.

Effect of cationic amino acid, L-lysine and its polymers on the growth and secretion of hybridoma cell line OKT-3.

Apart from their pivotal roles in anabolic protein synthesis, cationic amino acids, particularly, L-lysine HCl and its oligomers, up to molecular weight 1000, showed a remarkable property of cellular growth stimulation both in vitro and in vivo. L- and D-Lysine HCl, at a maximal stimulatory concentration of 7 microg/mL of added load of the amino acid, supported a characteristic time-scaled cellular expansion in vitro, and L-lysine-mediated cell expansion in batch cultures always showed a stimulation index (S.I.) ranging up to approximately 35, compared with the matched control populations. Variable S.I. was possibly due to factors such as seeding density, type of media additives, number of passages the cells have undergone before being stimulated, etc. Beyond and before maximal stimulatory concentration of the amino acid, there is a sharp decline in the cellular growth-promoting activity of monomeric L-lysine HCl in vitro, thereby showing a clear concentration window for maximum cellular growth promotion. While the essential amino acid does not have any dedicated cell surface receptor, the monomeric and oligomeric amino acid molecule(s) possibly mediates the serum-derived growth factor-receptor binding on the cell membrane by having two cationic charge centres at two ends of the molecule. Beyond a cutoff molecular weight of 1000, oligomeric lysines did not show any positive effects on either cell division and secretion.