The production of fish larvae is often hampered by high mortality rates, and it is believed that most of this economic loss due to infectious diseases is ca. 10% in Western European aquaculture sector. The development of strategies to control the pathogen load and immuno-prophylactic measures must be addressed further to realise the economic “potential” production of marine fish larvae and thus improve the overall production of adult fish.
The innate defence includes both humoral and cellular defence mechanisms such as the complement system and the processes played by granulocytes and macrophages. A set of different substances such as β-glucans, bacterial products, and plant constituents may directly initiate activation of the innate defence mechanisms acting on receptors and triggering intracellular gene activation that may result in production of anti-microbial molecules. These immunostimulants are often obtained from bacterial sources, brown or red algae and terrestrial fungi are also exploited as source of novel potentiating substances.
The use of immunostimulants, as dietary supplements, can improve the innate defence of animals providing resistance to pathogens during periods of high stress, such as grading, reproduction, sea transfer and vaccination. The immunomodulation of larval fish has been proposed as a potential method for improving larval survival by increasing the innate responses of the developing animals until its adaptive immune response is sufficiently developed to mount an effective response to the pathogen. To this end it has been proposed that the delivery of immunostimulants as a dietary supplement to larval fish could be of considerable benefit in boosting the animals innate defences with little detriment to the developing animal. Conversely, there is a school of thought that raises the concern of immunomodulating a neotanous animal before its immune system is fully formed as this may adversely affect the development of a normal immune response.
1.1. Immunostimulants in commercial aquaculture
According to Sakai  immunostimulants can be divided into several groups depending on their sources: bacterial, algae-derived, animal-derived, nutritional factors as immunostimulants, and hormones/ cytokines.
This sub-grouping is independent of their mode of action. A former definition of immunostimulants that restricted the target cells to be mononuclear phagocyte system  only should be redefined in view of recent discoveries of the pattern recognition receptors (PRRs). Different leucocytes may possess different PRRs and may bring about different immunological responses dependent on the binding receptor and intracellular signalling events. As such, a new definition must include all elements of the immune system and the definition could be ‘‘An immunostimulant is a naturally occurring compound that modulates the immune system by increasing the host’s resistance against diseases that in most circumstances are caused by pathogens’’. Although there is evidence for the beneficial use of immunostimulants in aquaculture, current commercial products are rather restricted in their formulation being derived from yeast, as in the case of b1-3, b1-6 glucans and sold under the Macroguard range of products e.g. MacroGard Immersion Grade, MacroGard AquaSol or MacroGard Adjuvant. Another successful commercial immunostimulant is Ergosan which is made from a seaweed-based meal rich in alginates and polysaccharides. A single dose of 1 mg of Ergosan significantly augmented the proportion of neutrophils, increased the degree of phagocytosis, respiratory burst activity and expression of interleukin-1b (IL-1b), interleukin-8 (IL-8) and one of the two known isoforms of trout tumour necrosis factor-alpha (TNF-a) in peritoneal leucocytes at 1 day post-injection . Humoral immune parameters were less responsive to intraperitoneal Ergosan administration with complement stimulation only evident in the 1 mg treated group at 2 days post-injection . The use of immunostimulants in vaccine formulations especially the b1-3, b1-6 glucans, experimentally at least, has given very good antibody responses when used either to replace oil based adjuvants, without the adverse side effects that have been reported for these types of adjuvants, or in addition to them [4e8].
With the discoveries of pattern recognition receptors the biological effects of a few immunostimulants have been studied. Although the output gene activation and the resulting production of pro-inflammatory cytokines have been studied there remains much research to systematise the effects of immunostimulants with regard to structureeactivity relationship, and the global effects the immunostimulants induce. In most cases, many intracellular signalling events that lead to e.g. disease protection caused by a certain immunostimulant have to be defined properly. Inevitably, many immunostimulants used in fish experiments induce beneficial effects such as disease protection due to increased cellular and humoral responses. However, cautions have to be taken regarding issues such as tolerance, non-wanted side effects such as immunosuppression using too high doses of immunostimulants or non-desirable effects caused by a prolonged use of such compounds. It is hoped that following the development of genomic and proteomic tools for several fish species, many issues with special attention to immune response polarisation after receptor binding of immunostimulants will be unveiled.